Phospholyl(borane) Amino Acids and Peptides: Stereoselective

Article pubs.acs.org/JACS

Cite This: J. Am. Chem. Soc. 2018, 140, 1028−1034

Phospholyl(borane) Amino Acids and Peptides: Stereoselective Synthesis and Fluorescent Properties with Large Stokes Shift Mathieu Arribat,† Emmanuelle Rémond,*,† Sébastien Clément,‡ Arie Van Der Lee,§ and Florine Cavelier*,† †

Institut des Biomolécules Max Mousseron, IBMM, UMR 5247, CNRS, Université de Montpellier, ENSCM, Place Eugène Bataillon, 34095 Montpellier cedex 5, France ‡ Institut Charles Gerhardt Montpellier, ICGM, UMR 5253, CNRS, Université de Montpellier, ENSCM, Place Eugène Bataillon, 34095 Montpellier cedex 5, France § Institut Européen des Membranes, IEM, UMR 5635, CNRS, Université de Montpellier, ENSCM, Place Eugène Bataillon, 34095 Montpellier cedex 5, France S Supporting Information *

ABSTRACT: The synthesis of phospholyl(borane) amino acids was stereoselectively achieved by reaction of phospholide anion with iodo α-amino ester derived from L-aspartic acid or Lserine, followed by in situ complexation with borane. Phospholyl(borane) amino acids are easy to store and can be subjected to direct transformation into the corresponding free phospholyl, gold complex, oxide or sulfur derivatives as well as phospholinium salts, thus offering a variety of side chains. After selective deprotection of carboxylic function or amine, C- or Npeptide coupling with an alanine moiety proved the possible incorporation into peptides. Such phospholyl amino acid and peptide derivatives exhibit fluorescent properties with a large Stokes shift (160 nm) and fluorescence up to 535 nm, depending on the phosphole aromaticity and the chemical environment. These phospholyl(borane) amino acids constitute a new class of unnatural amino acids useful for structure−activities relationship studies and appear to be promising fluorophores for the development of labeled peptides.

■

INTRODUCTION Unnatural amino acids with structure derived from natural compounds or designed by chemists are widely used for peptidomimetism, mainly because they provide resistance toward proteolitic degradation.1 Their structural and functional diversities are unlimited, thus offering modulation of steric hindrance, polarity, and conformational capabilities.2−4 Molecular imaging techniques are now indispensable tools providing biological information at the molecular level in living systems. In this context, a remarkable advance of fluorescence technique was illustrated by the visualization of protein-receptors using a greenfluorescent protein as tag, and was awarded by the Nobel Prize in 2008.5−7 Much efforts were also dedicated to the development of optical imaging for diagnosis and guided-treatment based on fluorescence emission in near-infrared (680−1300 nm) that did not interfere with the background due to the tissues auto fluorescence.8−11 Extended aromatic and heteroaromatic moieties can be exploited as fluorogenic and bright probes for multicolor imaging in biology or medicine.12−14 In the field of peptides tagging, fluorescent α-amino acids (FlAAs) have emerged beside prosthetic groups.15 They present the unique advantage of allowing their incorporation in specific position in a © 2017 American Chemical Society

peptide sequence, minimizing perturbations introduced by their presence compared to the native target.16,17 These chemical tools have also been incorporated in protein to monitor site-specific interactions with solvatochromic strategy18−20 and exploited for Fö rster resonance energy transfer (FRET) interactions.21 Peptide screening method using libraries with FlAAs proved to be useful for detecting peptides that bind to a target protein by fluorescence.22,23 Most of the FlAAs have been developed for peptides labeling and exhibit emission in the range of 400−550 nm.15 To prepare FlAAs, the fluorophore moiety is usually linked via a functional group of the side chain (NH 2 , SH, CO2H)16,17,24,25 or via a nonhydrolyzable covalent C−C bond,26−29 as illustrated by the examples 1−6 (Figure 1). The structure is designed according to the requested solubility and photophysical properties such as lifetime sensitivity to environment, absorption and emission wavelengths or high quantum yields.30 Typical examples are FlAAs derived from propionyl-dimethylaminonaphtalene 1, dimethylaminonaphtalimide 2 or coumarine 3,15,20,27 from tetramethylrhodamine Received: October 18, 2017 Published: December 20, 2017 1028

DOI: 10.1021/jacs.7b10954 J. Am. Chem. Soc. 2018, 140, 1028−1034

Article

Journal of the American Chemical Society

copper reagent with a chlorodibenzophosphole44 or by substitution with a dimethylphospholide salt.45 Compound 9 was obtained by palladium-catalyzed cross-coupling reaction of a 4-iodo-phenylalanine derivative with a stannylphosphole reagent.46 In all cases, phospholyl amino esters were isolated as sulfur derivatives, more stable than the free P(III)-product which was easily degraded under the reaction conditions. However, desulfurization of such compounds into free P(III)-phosphole could be performed by heating in the presence of tris(cyanoethyl)phosphine47 or using a nickel-catalyzed reducing process,48 but these conditions are not compatible with protecting groups and racemization-free peptide chemistry. In addition, no details are reported on the enantiomeric purity of these thiophospholyl amino acid derivatives. In continuation of phosphorus, boron and amino acid chemistry we previously investigated,49,50 we were interested in synthesizing phospholyl(borane) amino acid derivatives as new class of unnatural amino acids with fluorescent properties. Several derivatives by oxidation, sulfuration or quaternization of the P-center as well as phospholyl(borane) dipeptides are also described. The spectroscopic analysis of phospholyl amino acids revealed large Stokes shift and fluorescence emission up to 535 nm, depending either on the phosphole aromaticity and of the substituent born by the phosphorus atom.

Figure 1. Selection of fluorescent amino acids with high λem.

(TMR)22,23 4 or BODIPY-based dyes 5,28 or still from functionalized tyrosine 6.29 In all cases, the FlAAs with high wavelength emission show a large aromatic moiety bearing electron-withdrawing and -donating, ionizable or highly polarized substituents (Figure 1). It is clearly important to develop FlAAs not derived from dyes with long emission wavelengths and huge steric hindrance, and which can be easily modified to perfect the fluorescent properties and used in peptide synthesis without changing structure and stereoelectronic properties dramatically. Among fluorophores, phosphole moieties are intensively studied for the development of electronic flexible devices such as organic light emitting diodes (OLEDs).31−34 The phosphole is a weakly aromatic five membered heterocycle, having the characteristics of a dienic system bridged with a tetrahedric phosphorus atom that allows easy chemical modifications by oxidation, sulfuration, alkylation and complexation to afford suitable derivatives with tunable electroluminescent properties.31−34 While few examples of phosphole borane were described to date, fluorescent properties of 3,5-conjugated derivatives have been highlighted in the development of organic optoelectronic materials.33,35−39 Preparing phospholes amino acid and peptides derivatives represents a promising approach to modulate their photophysical properties since amino acid and peptide side chains can direct the self-assembly of π-conjugated scaffold into ordered nanostructures.40−43 Until to date, only the synthesis of thiophospholyl amino acid derivatives such as 7−9 have been reported (Figure 2).44−46 The synthesis of compounds 7 and 8 was achieved from βiodoserine methyl ester by reaction of the corresponding zinc/

■

RESULTS AND DISCUSSION Synthesis of Phospholyl(borane) α-Amino Esters. The stereoselective synthesis of phospholyl(borane) α-amino esters 12a−e was achieved by substitution of β- or γ-iodo amino esters 11a−e with phospholide reagents 10′ followed by addition of borane dimethyl sulfide (BH3·DMS) to the reaction mixture (Table 1). The iodo amino esters 11a−e, bearing selected protecting groups suitable for peptide synthesis Allyl (All), Benzyl (Bn), t-butyloxycarbonyle (Boc) were previously prepared from L-aspartic acid and L-serine, respectively.49,51 Table 1. Stereoselective Synthesis of Dibenzophospholyl(borane) Amino Esters 12a−e

entry

preparation of phospholidea,b

iodo amino ester

borane complex

yield (%)c,d

1 2 3 4 5 6 7 8

n-BuLi LDA NaH KHMDS KHMDS KHMDS KHMDS KHMDS

11a 11a 11a 11a 11b 11c 11d 11e

12a 12a 12a 12a 12b 12c 12d 12e

10 26 47 74 70 68 78 70

Base was added to a solution of dibenzophosphole 10 at −78 °C, 45 min. 11a−e were added at −78 °C, 45 min. b1.3 equiv of 10 were used. cIsolated yields after purification by flash chromatography. de.e. values of phospholyl(borane) amino esters 12a−e were determined by HPLC on chiral column. a

Figure 2. Thiophospholyl amino acid derivatives. 1029


Article


X-ray Structure of the Phospholyl(borane) Amino Ester 12d. The structure of the dibenzophospholyl(borane) amino ester 12d was determined by single crystal X-ray diffraction analysis (Figure 3). This compound crystallized in the non-

The phospholide reagent 10′ was prepared by deprotonation of the corresponding phosphole 10. Under these conditions, the phospholyl(borane) L-α-amino ester derivatives 12a−e were isolated in good to excellent yields (Table 1) as stable compounds, easy to store and to handle for further use. When n-butyllithium (n-BuLi), lithium diisopropylamide (LDA) or sodium hydride (NaH) were used as base, the substitution of the iodide 11a, followed by in situ complexation of the P-center with BH3·DMS, afforded the dibenzophospholyl(borane) amino ester 12a in low to moderate yields from 10 to 47% (entries 1−3). The highest yield of 74% was obtained when potassium bis(trimethylsilyl)amide (KHMDS) was used as base (entry 4). It should be noted that when the reaction mixture was quenched by hydrolysis without complexation, the phospholyl intermediate was isolated as oxide derivative, proving its extreme sensitivity to oxidation in these conditions. Under these optimized conditions, the substitution of the N-Boc-γ-iodo amino ester 11b with the dibenzophospholide 10′ led to the corresponding phospholyl(borane) amino ester 12b in 70% yield and 99% e.e. (entry 5). The reaction with the dibenzophospholide 10′ was also performed on β- and γ-iodo amino allyl esters 11c−e, affording the corresponding phospholyl(borane) complexes 12c−e in 68 to 78% isolated yields (entries 6−8). The reaction was extended to the 3,4-dimethylphospholide 13′, obtained by P−C bond cleavage of the corresponding phosphole 13 with potassium.52 Phospholide anion 14′ was also obtained by P−C bond cleavage of phenyl phosphole 14, which was in situ generated by treatment of the open-chain acetylenic phosphine in the presence of potassium excess.53 The reaction of phospholide 13′ with 11d and 11e led to the corresponding 3,4dimethylphospholyl(borane) amino esters 16a and 16b in 60% and 63% yields and 98% e.e. (Scheme 1).

Figure 3. Molecular structure of 12d in the solid state (50% probability level). Selected bond lengths [Å] and angles: P1−C2 1.807(3); P1−C9 1.818(3); P1−C14 1.822(2); P1−B31 1.906(3); C14−P1−B31 109.91(15); C2−P1−C9 91.45(13); C2−P1−C14 109.36(13); C9− P1−C14 108.21(13); C2−P1−B31 117.64(17); C9−P1−B31 118.79(18); C3−C2−P1−C9−2.6(5); C7−C2−P1−B31 −50.9(8); C7−C2−P1−C14 75.4(6); C9−C8−C3−C2 −3.5(6).

centro-symmetric P212121 group, and the Flack55 parameter refinement allowed us to determine the (S)-absolute configuration at the carbon atom unambiguously. This configuration is in good agreement with that of the starting product 11d. In addition, the structure of 12d shows a distorted tetrahedral geometry at the P atom with a P−B bond of 1.906 Å which is typical of phosphine borane adducts.56 A statistical analysis of all the distances, angles and torsion angles compared to the structures found in the Cambridge Structural Databank, confirms that the length of the P−B bond is typical (1.906 Å vs 1.912 Å in average) (see SI). The dibenzophosphole moiety exhibits a flat five membered ring characterized with a C3−C2−P1−C9 dihedral angle of −2.6(5)° (Figure 3). Consequently, the PBH3 and P-CH2 groups are on each side of the phosphole ring with C7−C2−P1−B31 and C7−C2−P1−C14 dihedral angles of −50.9(8)° and 75.4(6)° respectively. Chemical Transformations at the P-Center. The phospholyl(borane) amino ester 12d was successfully transformed into the free phosphole 19 by decomplexation of the borane with 1,4-diazabicyclooctane (DABCO).57 In addition, the phospholyl(oxide) 20, and the phospholyl(sulfide) 21 were obtained in 68 and 90% yield by in situ reaction either with tertbutyl hydroperoxide or sulfur respectively, in the presence of DABCO (Scheme 2a). Phospholyl gold chloride complex 22 was obtained in 90% yield after decomplexation of 12d by DABCO, then reaction of the resulting free phospholyl amino ester with AuCl·DMS. On the other hand, quaternization with methyl iodide was achieved by heating the dibenzophospholyl(borane) complex 12d in the presence of octene to afford the corresponding dibenzophospholinium salt 23 in 79% isolated yield (Scheme 2b). The enantiomeric purity of phospholyl amino esters 19−22 was checked by chiral HPLC by comparison with a racemic sample. In the case of the phospholium salt bearing allyl ester 23, the enantiomeric purity was checked by 31 1 P{ H} NMR using the hexacoordinated phosphorus BINPHAT anion as chiral reagent (see SI).58 The phosphindolyl-

Scheme 1. Synthesis of Phospholyl(borane) Amino Esters 16d,e, 17d, 18d from Phenyl Phospholes 13−15a,b,c

a

Reactions were performed in Schlenk tubes. See SI for workup procedures. bIsolated yields. ce.e. values of phospholyl(borane) amino esters 16a,b, 17, 18 were checked by HPLC on chiral column.

When 11d was reacted with phospholide 14′ prepared from 14, the phospholyl(borane) 17 was obtained in 35% yield as an epimeric mixture in ratio 4:1 due to the P-chirogenic center. Finally, when 11d reacted with binaphtolyl anion 15′ obtained by potassium-mediated P−C bond cleavage54 of the naphtyl phosphole 15, the corresponding binaphtylphospholyl(borane) amino ester 18 was isolated in 50% yield and 98% e.e. The enantiomeric purity of all phospholyl(borane) amino esters was checked by chiral HPLC by comparison with a racemic sample (see SI). 1030


Article


coupling reaction using HATU, DIPEA in DMF. No reaction was observed, only degradation due to free amine in DMF. Traces of dipeptides 29 and 31 were observed in THF or DCM in the presence of different coupling agent (HATU, HBTU, CDI) with N,N-diisopropylamine (DIPEA) as base. Only isobutyl chloroformate (IBCF) gave low conversion (about 30%) at 0 °C. Interestingly, the use of cesium carbonate (Cs2CO3) in dichloromethane (DCM) with HATU as coupling agent afforded the desired compounds (Scheme 3a and b). Indeed, such inorganic base not soluble in DCM, avoid the use of amines which degrade the borane complex and consequently, lead to a dramatic decrease in the coupling yields. Under these conditions, the corresponding dibenzophospholyl(borane) dipeptide 29 was obtained diastereomerically pure in 65% isolated yield (Scheme 3a). It is worth noting that the free dibenzophospholyl dipeptide 29′ could be obtained in 66% yield by decomplexation of 29 with DABCO (see SI). Besides, the coupling reaction between dibenzophospholyl(borane) N-Bocamino acid 27 with the HCl·H-L-Ala-OMe 30 leads to the corresponding dipeptide 31 in 50% yield (Scheme 3b). After deprotection of the amino group of dipeptide 29, stability of the corresponding hydrochloride salt was studied in phosphate buffer at pH = 7.4. No oxidation or decomplexation was observed by 31P{1H} and 11B{1H} NMR during 7 h (see SI). The solid phase peptide synthesis (SPPS) at a 0.05 mmol scale using Fmoc-L-Ala preloaded Wang resin 32 and dibenzophospholyl sulfide Fluorenylmethyloxycarbonyl (Fmoc) amino acid 33, previously prepared from the free phospholyl sulfide amino acid, was also demonstrated. HATU was used as coupling agent in the presence of NEt3. Deprotection cycles were carried out using 20% piperidine in DMF. N-Coupling between the dipeptide 34 and Fmoc-L-Ala-OH 35 was performed under the same conditions, followed by final cleavage of 36 from the resin with CH2Cl2/TFA (1:1) to afford the corresponding tripeptide 37 in 58% yield (Scheme 4).

Scheme 2. Synthesis of the Dibenzophospholyl Amino Esters 14a,b

a Isolated yields after purification by flash column chromatography for 19−22 and 24, 25 or precipitation for 23. be.e. values were checked by HPLC on chiral column for 19−22, 24, 25 and by 31P{1H} NMR with BINPHAT counteranion for 23.

(sulfide) 24 and binaphtylphospholyl(sulfide) 25 were prepared in yields up to 64%, by reaction of a mixture sulfur/DABCO starting from the corresponding borane complexes 17 or 18 respectively. Synthesis of Dibenzophospholyl(borane) Peptide Derivatives. The phospholyl(borane) amino ester 12d was selectively deprotected in order to check the compatibility of such complex in regard to peptide coupling conditions (Scheme 3). Deprotection of the amino group was achieved by treatment Scheme 3. Synthesis of Dibenzophospholyl(borane) Dipeptide Derivatives

Scheme 4. Solid Phase Peptide Synthesis (SPPS) with FmocProtected Dibenzophospholyl(sulfide) Amino Acid 33

with HCl (4 M) in dioxane at room temperature to afford the phospholyl(borane) amino ester as hydrochloride salt 26 in 73% yield without racemization. First attempts to release the free carboxylic acid function starting from dibenzophospholyl(borane) benzyl ester 12a and 12b either by hydrogenolysis catalyzed by palladium or by saponification with lithium hydroxide (LiOH) were unsuccessful, the starting material being recovered or oxidized. However, the reaction of allylic ester 12d with sodium borohydride (NaBH4) afforded the corresponding dibenzophospholyl(borane) derivative 27 bearing the free carboxylic acid in 78% yield without racemization.59 The feasibility of peptide coupling in the presence of phospholyl(borane) moiety 26 or 27 with alanine derivative as model (28 or 30 respectively) was investigated by classic

Photophysical Properties. Until to date, the fluorescence properties of phospholyl(borane) have been scarcely reported, being limited to aromatic, furyl or thienyl substituents. In these cases, the contribution of the molecular orbital of the aromatic substituents to the excited transition state allows straightforward fine-tuning of the gap and thus, the overall optical properties. In contrast, surprisingly, the fluorescence of small phospholyl(borane) at above 600 nm was not clearly reported. Consequently, we decided to examine in more details the photophysical properties of compounds 12a,b; 16a,b−25 and 29 by combining UV−vis and fluorescence spectroscopies. Table 2 1031


Article

Journal of the American Chemical Society Table 2. Photophysical Data of Phospholyl Derivatives

a

entry

compound

λabs (nm)a

λex (nm)a

λem (nm)a

Stokes shift (nm)

Φ (%)a

1 2 3 4 5 6 7 8 9 10 11 12 13 14

12d 12e 16a 16b 17 18 19 20 21 22 23 24 25 29

275, 286, 310 277 (sh),c 287 (sh) 290, 300 278, 290, 300 (sh) 278, 282, 290, 300 255, 265, 305, 335 (sh), 350, 380 247 (sh), 276, 281, 303, 317 247, 275 (sh), 282, 292, 330 274, 279, 293, 301, 328 243, 281, 290, 303, 323 243, 281, 290 (sh), 335 246, 294, 305 (sh), 340 256, 265, 335 (sh), 346, 375 246, 274 (sh), 281, 292, 328

270 290 290 290 325 320 290 270 320 290 270 325 325 270

343 354 353 356 416 435 357 360 375 353 376 420 535 360

33 67 53 56 116 55 40 30 47 30 41 80 160 32

10 5 ndb ndb 16 35 7 30 1 9 8 2 3 25

Measured in CH2Cl2 at 25 °C. bToo low to be determined. csh: shoulder.

summarizes the obtained data for the phospholyl amino acid derivatives in CH2Cl2. The absorption spectra of phospholyl(borane) amino ester 12d, free phospholyl 19, oxide, sulfide, gold complex and phospholium derivatives 20−23 are depicted in Figure 4. Similar

Figure 5. Normalized emission spectra of dibenzophospholyl amino esters in CH2Cl2: 12d (borane complex) and 19−23 (lone pair, oxide, sulfide, gold chloride complex and phospholium salt) recorded at 5 × 10−5 M.

The optical properties of these phosphole derivatives were also found to be sensitive to the size and the nature of the πconjugated scaffold. Compared to dibenzophospholyl(borane) 12d and phosphindolyl(borane) 17, the absorption spectrum of binaphtylphospholyl(borane) derivative 18 is significantly redshifted with the appearance of a new absorption band centered at 370 nm (Figure 6). The increase of the conjugation length and/ or the aromaticity from 12d to 17 and 18 decreases the gap between HOMO and LUMO (π−π*) leading respectively to red-shifted emission of 73 and 92 nm (Figure 7) and lead to higher quantum yields up to 35% (for naphtyl phosphole 18) (Table 2). These higher quantum yield values indicate significantly lowered nonradiative deactivation.60 Since a higher emission wavelength was observed for the phospholyl sulfide derivative 21 (λem = 375 nm) in the dibenzophospholyl amino ester series, we recorded the emission spectra of phosphindolyl sulfide 24 and binaphtylphospholyl sulfide 25 in CH2Cl2. While a small bathochromic effect of (4 nm) was observed for 24 compared to its borane derivative 17 (see Supporting Information), 25 exhibits a remarkable redshifted emission at λem = 535 nm with a large Stokes shift of 160 nm (Figure 8 and Table 2). The absorption spectra of the dibenzophospholyl(borane) 12d were also recorded in AcOEt, EtOH, DMF and THF. The same UV profile was observed compared to CH2Cl2 (Figure 9). A

Figure 4. UV−vis absorption spectra of dibenzophospholyl amino esters in CH2Cl2: 12d (borane complex) and 19−23 (lone pair, oxide, sulfide, gold chloride complex and phospholium salt) recorded at 2.5 × 10−5 M, 5 × 10−5 M, 1.66 × 10−5 M, 2.5 × 10−5 M, 2.5 × 10−5 M, 5 × 10−5 M, respectively.

absorption features in 250−350 nm region were observed for all these compounds with molar absorption coefficients (ε) between 6500 and 24 000 L mol−1 cm−1 (Table 2). The fluorescence spectra of phospholyl amino ester 12d and 19−23 were then collected by excitation (λex) in the higher wavelength absorption band (i.e., λex = 270−320 nm) (Figure 5 and Table 2). All these compounds are fluorescent in solution with a gradual red shift of λem values in the following order: P-oxide 20 < Psulfide 21 < phospholium salt 23, indicating that the nature of the substituent on the phosphole lone pair allows fine-tuning of the emission properties of phospholyl amino acid derivatives.31−34,46,47 Compared to the relatively high quantum yield of the dibenzophospholyl oxide 20 (Φϕ = 0.30), the values for free phosphorus 19, sulfide derivative 21 and phospholium 23 are lower: Φf = 0.07, 0.01 and 0.08, respectively (Table 2). 1032


Article


Figure 9. Normalized UV−vis absorption (plane) and normalized emission (dot) spectra of dibenzophospholyl amino ester 12d in various solvents at 5 × 10−5 M.

Figure 6. UV−vis absorption spectra in CH2Cl2 of dibenzophospholyl(borane) amino esters 12d, 16a, 17 and 18 recorded at 2.5 × 10−5 M, 5 × 10−5 M, 5 × 10−5 M, 1.66 × 10−5 M, respectively.

Interestingly, we showed that the phospholyl(borane) complexes can be easily transformed into the corresponding free phospholyl amino ester, phospholinium salts, oxide, sulfur derivatives, as well as gold chloride complex, without racemization. In addition, free carboxylic acid and amine derivatives were obtained by reduction or acidolysis of phospholyl(borane) N-Boc-amino esters, respectively. The C- or N- peptide coupling was demonstrated by reaction of the phospholyl(borane) compounds with an alanine residue. Phospholyl(borane) amino esters and dipeptides exhibit remarkable fluorescence with emission and Stokes shift up to 535 nm (green) and 160 nm, respectively appearing as promising candidates for the fluorescent labeled peptides. Furthermore, the introduction of phospholyl(borane) amino acid residues in peptide chains offers the opportunity to direct the spatial orientation and the packing of these functional conjugated organophosphorus molecules61,62 and thus, to tune the photophysical and electronic properties, making them wellsuited for bioelectronic applications. As such, the self-assembly of these phospholes63−65 appended with amino acid derivatives deserves further investigation and will be reported in due course.

Figure 7. Normalized emission spectra in CH2Cl2 of dibenzophospholyl amino ester 12d, 16a, 17 and 18 recorded at 5 × 10−5 M.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.7b10954. Crystal data (CIF) Experimental part; NMR spectra; Absorption-normalized emission spectra; Chiral HPLC chromatograms (PDF)

■

AUTHOR INFORMATION

Corresponding Authors

Figure 8. Absorption/normalized emission spectra of binaphtylphospholyl amino ester 25 in CH2Cl2 recorded at 2.5 × 10−5 M.

*[email protected] *fl[email protected]

small bathochromic shift was noted for λem in AcOEt, THF and EtOH in regards to CH2Cl2 (Δλem = 1 to 4 nm), while in DMF, it increases to 357 nm (Δλem = 14 nm) (Figure 9).

ORCID

CONCLUSION New phospholyl(borane) amino acid and peptide derivatives were stereoselectively synthesized by P−C bond formation. The synthesis proceeds through the reaction of phospholide anions with iodo α-amino ester derived from L-aspartic acid or L-serine, followed by in situ addition of borane as complexing agent.

Notes

Emmanuelle Rémond: 0000-0002-3201-4365 Sébastien Clément: 0000-0002-8473-8197 Florine Cavelier: 0000-0001-5308-6416

■

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS We thank Montpellier University for the grant to Mathieu Arribat. 1033


Article


■

(41) Zhou, Y.; Li, B.; Li, S.; Ann, H.; Ardoña, M.; Wilson, W. L.; Tovar, J. D.; Schroeder, C. M. ACS Cent. Sci. 2017, 3, 986. (42) Li, B.; Li, S.; Zhou, Y.; Ardon, H. A. M.; Valverde, L. R.; Wilson, W. L.; Tovar, J. D.; Schroeder, C. M. ACS Appl. Mater. Interfaces 2017, 9, 3977. (43) Lehrman, J. A.; Cui, H.; Tsai, W.-W.; Moyer, T. J.; Stupp, S. I. Chem. Commun. 2012, 48, 9711. (44) Agarkov, A.; Greenfield, S.; Xie, D.; Pawlick, R.; Starkey, G.; Gilbertson, S. R. Biopolymers 2006, 84, 48. (45) Zutphen, S. V.; Margarit, V. J.; Mora, G.; Le Floch, P. Tetrahedron Lett. 2007, 48, 2857. (46) Bisaro, F.; Le Floch, P. Synlett 2010, 20, 3081. (47) Deschamps, E.; Mathey, F. Bull. Soc. Chim. Fr. 1992, 129, 486. (48) Gilbertson, S. R.; Chen, G.; McLoughlin, M. J. Am. Chem. Soc. 1994, 116, 4481. (49) Rémond, E.; Bayardon, J.; Ondel-Eymin, M. J.; Jugé, S. J. Org. Chem. 2012, 77, 7579. (50) Rémond, E.; Bayardon, J.; Takizawa, S.; Rousselin, Y.; Sasai, H.; Jugé, S. Org. Lett. 2013, 15, 1870. (51) Koseki, Y.; Yamada, H.; Usuki, T. Tetrahedron: Asymmetry 2011, 22, 580. (52) Holand, S.; Mathey, F.; Fischer, J.; Mitschler, A. Organometallics 1983, 2, 1234. (53) Xu, Y.; Wang, Z.; Gan, Z.; Xi, Q.; Duan, Z.; Mathey, F. Org. Lett. 2015, 17, 1732. (54) Gladiali, S.; Dore, A.; Fabbri, D.; De Lucchi, O.; Valle, G. J. Org. Chem. 1994, 59, 6363. (55) Flack, H. D. Acta Crystallogr., Sect. A: Found. Crystallogr. 1983, 39, 876. (56) Brunel, J. M.; Faure, B.; Maffei, M. Coord. Chem. Rev. 1998, 178− 180, 665. (57) Dutartre, M.; Bayardon, J.; Jugé, S. Chem. Soc. Rev. 2016, 45, 5771. (58) Hebbe, V.; Londez, A.; Goujon-Ginglinger, C.; Meyer, F.; Uziel, J.; Jugé, S.; Lacour, J. Tetrahedron Lett. 2003, 44, 2467. (59) Pawar, B. V.; Lokhande, P. D. Synth. Commun. 2009, 39, 2445. (60) Ren, Y.; Biegger, F.; Baumgartner, T. J. Phys. Chem. C 2013, 117, 4748. (61) Wang, Z.; Baumgartner, T. Chem. Rec. 2015, 15, 199. (62) Wang, Z.; Gelfand, B. S.; Dong, P.; Trudel, S.; Baumgartner, T. J. Mater. Chem. C 2016, 4, 2936. (63) Ardona, H. A. M.; Tovar, J. D. Bioconjugate Chem. 2015, 26, 2290. (64) Liyanage, W.; Ardona, H. A. M.; Mao, H.-Q.; Tovar, J. D. Bioconjugate Chem. 2017, 28, 751. (65) Besar, K.; Ardona, H. A. M.; Tovar, J. D.; Katz, H. E. ACS Nano 2015, 9, 12401.

REFERENCES

(1) Gentilucci, L.; De Marco, R.; Cerisoli, L. Curr. Pharm. Des. 2010, 16, 3185. (2) Stevenazzi, A.; Marchini, M.; Sandrone, G.; Vergani, B.; Lattanzio, M. Bioorg. Med. Chem. Lett. 2014, 24, 5349. (3) Blaskovich, M. J. Med. Chem. 2016, 59, 10807. (4) Rémond, E.; Martin, C.; Martinez, J.; Cavelier, F. Chem. Rev. 2016, 116, 11654. (5) Shimomura, O. Angew. Chem., Int. Ed. 2009, 48, 5590. (6) Chalfie, M. Angew. Chem., Int. Ed. 2009, 48, 5603. (7) Tsien, R. Y. Angew. Chem., Int. Ed. 2009, 48, 5612. (8) Su, H.; Wang, Z.; Liu, G. Cancer. Theranostics 2014, 55. (9) Berezin, M. Y.; Achilefu, S. Chem. Rev. 2010, 110, 2641. (10) Jameson, D. M.; Ross, J. A. Chem. Rev. 2010, 110, 2685. (11) Wegner, D. K.; Hildebrandt, N. Chem. Soc. Rev. 2015, 44, 4792. (12) Lavis, L. D.; Raines, R. T. ACS Chem. Biol. 2014, 9, 855. (13) Lukinavicius, G.; Reymond, L.; Umezawa, K.; Sallin, O.; D’Este, E.; Göttfert, F.; Ta, H.; Hell, S. W.; Urano, Y.; Johnsson, K. J. Am. Chem. Soc. 2016, 138, 9365. (14) Fernandez, A.; Vendrell, M. Chem. Soc. Rev. 2016, 45, 1182. (15) Krueger, A. T.; Imperiali, B. ChemBioChem 2013, 14, 788. (16) Katritzky, A. R.; Narindoshvili, T. Org. Biomol. Chem. 2009, 7, 627. (17) Pazos, E.; Vazquez, O.; Mascarenas, J. L.; Vazquez, M. E. Chem. Soc. Rev. 2009, 38, 3348. (18) Loving, G. S.; Sainlos, M.; Imperiali, B. Trends Biotechnol. 2009, 28, 73. (19) Hsieh, T.-y.; Nillegoda, N. B.; Tyedmers, J.; Bukau, B.; Mogk, A.; Kramer, G. PLoS One 2014, 9, e99935. (20) Sholokh, M.; Zamotaiev, O. M.; Das, R.; Postupalenko, V. Y.; Richert, L.; Dujardin, D.; Zaporozhets, O. A.; Pivovarenko, V. G.; Klymchenko, A. S.; Mély, Y. J. Phys. Chem. B 2015, 119, 2585. (21) Speight, L. C.; Muthusamy, A. K.; Goldberg, J. M.; Warner, J. B.; Wissner, R. F.; Willi, T. S.; Woodman, B. F.; Mehl, R. A.; Petersson, E. J. J. Am. Chem. Soc. 2013, 135, 18806. (22) Kitamatsu, M.; Futami, M.; Sisido, M. Chem. Commun. 2010, 46, 761. (23) Kitamatsu, M.; Yamamoto, T.; Futami, M.; Sisido, M. Bioorg. Med. Chem. Lett. 2010, 20, 5976. (24) Esteves, C. I. C.; Silva, A. M. F.; Raposo, M. M. M.; Costa, S. P. G. Tetrahedron 2009, 65, 9373. (25) Häubler, D.; Gütschow, M. Synthesis 2016, 48, 245. (26) Schmidt, L.; Doroshenko, T.; Barbie, P.; Grüter, A.; Jung, G.; Kazmaier, U. Synthesis 2016, 48, 3077. (27) Cohen, B. E.; McAnaney, T. B.; Park, E. S.; Jan, Y. N.; Boxer, S. G.; Jan, L. Y. Science 2002, 296, 1700. (28) Gusow, K.; Kornowska, K.; Wiczk, W. Tetrahedron Lett. 2009, 50, 2908. (29) Cheruku, P.; Huang, J.-H.; Yen, H.-J.; Iyer, R. S.; Rector, K. D.; Martinez, J. S.; Wang, H.-L. Chem. Sci. 2015, 6, 1150. (30) Maity, K. M.; Bera, S.; Haldar, D. Curr. Org. Synth. 2013, 10, 525. (31) Joly, D.; Tondelier, D.; Deborde, V.; Geffroy, B.; Hissler, M.; Réau, R. New J. Chem. 2010, 34, 1603. (32) Joly, D.; Tondelier, D.; Deborde, V.; Delaunay, W.; Thomas, A.; Bhanuprakash, K.; Geffroy, B.; Hissler, M.; Réau, R. Adv. Funct. Mater. 2012, 22, 567. (33) Stolar, M.; Baumgartner, T. Chem. - Asian J. 2014, 9, 1212. (34) Duffy, M. P.; Delaunay, W.; Bouit, P.-A.; Hissler, M. Chem. Soc. Rev. 2016, 45, 5296. (35) Baumgartner, T.; Bergmans, W.; Karpati, T.; Neumann, T.; Nieger, M.; Nyulaszi, L. Chem. - Eur. J. 2005, 11, 4687. (36) Baumgartner, T.; Wilk, W. Org. Lett. 2006, 8, 503. (37) Huy, N. H. T.; Donnadieu, B.; Mathey, F.; Muller, A.; Colby, K.; Bardeen, C. J. Organometallics 2008, 27, 5521. (38) Ren, Y.; Baumgartner, T. J. Am. Chem. Soc. 2011, 133, 1328. (39) Huy, N. H. T.; Lu, Y.; Qune, L. F. N. A.; Mathey, F. J. Organomet. Chem. 2013, 730, 63. (40) Ann, H.; Ardon, M.; Draper, E. R.; Citossi, F.; Wallace, M.; Serpell, L. C.; Adams, D. J.; Tovar, J. D. J. Am. Chem. Soc. 2017, 139, 8685. 1034


Phospholyl(borane) Amino Acids and Peptides: Stereoselective

Recommend Documents