Bioinspired Syntheses of Herqulines B and C from Cyclodipeptide

Subscriber access provided by TULANE UNIVERSITY

Communication

Bioinspired Syntheses of Herqulines B and C from Cyclodipeptide Mycocyclosin Xu Zhu, Christopher C. McAtee, and Corinna S. Schindler J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 14 Feb 2019 Downloaded from http://pubs.acs.org on February 14, 2019

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society

Xu Zhu‡, Christopher C. McAtee‡, and Corinna S. Schindler*. †

Willard Henry Dow Laboratory, Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States. Supporting Information Placeholder ABSTRACT: An approach for the syntheses of herqulines B and C is reported that takes advantage of an L-tyrosine-derived diketopiperazine, a mycocyclosin analog, as a synthetic precursor. The strategy relies on a series of consecutive reductions to adjust the mycocyclosin oxidation state to that observed in the herquline class of natural products. The strained and distorted L-tyrosinebased biaryl system characteristic for mycocyclosin is selectively converted to the 1,4-diketone structural motif common to the herqulines via initial hypervalent iodine-mediated dearomatization and a subsequent directed Birch reduction, enabled by an intramolecular H-source. Additionally, the piperazine oxidation state is accessible via an iron-catalyzed reduction of a diketopiperazine intermediate.

Forty years ago, Ōmura reported the isolation of the fungal metabolite herquline A (1),1 a strained pentacyclic piperazine, from Penicillium herquei Fg-372 (Fig. 1A). Herquline A (1) was shown to prevent platelet aggregation1 in addition to displaying antibiotic properties by inhibiting replication of the influenza virus.2 The structurally related tetracyclic piperazine herquline B (2)3 was isolated in 1996 although its absolute configuration could only recently be determined upon the completion of the first synthesis by Wood4a and Baran.4b The structure of a third congener, herquline C (3),5 was isolated in 2016 by Houk and Tang during studies of the herquline biosynthetic pathway and identified as a diastereomer of herquline B (2) by Wood in 20184a. All three herqulines are characterized by a highly strained macrocyclic scaffold, a piperazine moiety, and a 2,3-disubstituted 1,4-dicarbonyl subunit (11 and 11a in 2-3) that has historically proven remarkably problematic to access synthetically.6 Reported synthetic efforts towards the herqulines corroborate these challenges:7 specifically, intramolecular coupling reactions to form the 1,4-diketone subunit are hampered by the ring strain imparted by the macrocycle, while macrocyclic ring closure to forge the piperazine ring after installation of the 1,4-diketone scaffold has proven to be equally difficult. Our interest in these natural products started with the isolation of mycocyclosin (4),8,9 a strained diketopiperazine dipeptide derived from cyclodityrosine cYY (5), which was initially hypothesized to be a biosynthetic precursor for the herqulines (Fig. 1B)10, 11. Despite the distinct biological genesis of mycocyclosin (4) and the herqulines A-C (1-3), we were intrigued by the inherent symmetry of these molecules and envisioned that a viable synthetic route could rely on selective reduction of the mycocyclosin core. Specifically, we considered the reduced mycocyclosin analog 6 as a common precursor to develop a viable route towards the herquline natural products (Fig. 2). Although the C2-symmetric piperazine 6 was expected to significantly facilitate synthetic efforts, four key challenges remained: (1) a scalable synthetic route to access gram-

Figure 1. A. L-tyrosine-derived natural products herqulines A-C (1-3) and mycocyclosin (4). B. Initial biosynthetic hypothesis for the formation of herqulines A-C from mycocyclosin. quantities of the strained cyclophane (4) or a related analog; (2) the development of a reliable protocol for diketopiperazine reduction in strained macrocycles; (3) a viable dearomatization strategy for highly strained and distorted biaryl systems11,12 to selectively provide (4) the ,-enone over the corresponding ,-enone structural motifs. With these challenges in mind, we first focused on the development of a robust synthetic strategy to obtain gram-quantities of mycocyclosin (4). Pioneering work by Hutton in 201211 had shown that a Pd-catalyzed Suzuki-Miyaura cross-coupling resulted in mycocyclosin macrocyclization in 42% yield on a 50 mg scale. Although a crucial advance, these reaction conditions were not amenable to larger scales and access to cyclophane 4 remained limited. In initial studies, we were able to build on the results of Hutton and coworkers to develop a scalable and reproducible synthesis of mycocyclosin (4).12 Our detailed investigations of the cross-coupling conditions had revealed beneficial effects of H2O and exogenous air on the macrocyclization yield obtained. Based on these results,

ACS Paragon Plus Environment

Journal of the American Chemical Society 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 2. Initial hypothes for a synthetic strategy towards herqulines A-C (1-3) based on the inherent C2-symmetry of piperazine 6. we considered a mechanism initiated by a palladium(II) peroxy species13 formed upon oxidation of palladium(0) and water as a crucial additive to aid the formation of a palladium(II) hydroxyl complex to ultimately intercept the Suzuki-Miyaura reaction pathway.12 With a scalable synthetic strategy towards mycocyclosin secured, we next evaluated approaches to effect the selective reduction of the biaryl subunit. We were particularly inspired by Laguzza and Ganem who reported the formation of ,-enone 9 upon Birch reduction of N,N-diallyl-O-methyl-L-tyrosine (7) and subsequent aqueous hydrolysis of diene 8 (Fig. 3A).14 However, Birch reduction of biaryl 10 formed 1,3-diene 12 exclusively, presumably upon isomerization of the desired 1,4-diene 11. Subsequent acidic hydrolysis of diene 12 resulted in ,-enone 13, and X-ray crystallographic analysis confirmed the formation of the undesired regiosiomer. Ensuing efforts focused on the evaluation of additional Birch reduction conditions15,16 of biaryl 10 or its diketopiperazine analog, though the preferred regioselectivity could not be overturned and the formation of skipped diene 11 was never observed. Additionally, investigation of exogenous proton sources such as tBuOH led to the isolation of overreduction products together with diene 12. Moreover, the second aromatic ring in biaryl 10 proved unreactive in the Birch reduction16 which prompted us to consider alternative strategies for dearomatization. Ultimately, succeeding studies identified reaction conditions relying on hypervalent iodine reagents17 as complementary and capable of providing the desired regioisomer of ,-enone 13 upon reaction with biaryl 10. With a viable route to mycocyclosin secured and promising initial studies for dearomatization of the biaryl system completed, we set out to develop a robust synthetic route to the herquline natural products (Fig. 4). The L-tyrosine dipeptide 16 is readily available in 83% yield under standard peptide coupling reactions from Ltyrosine derivatives 14 and 15. Trifluoroacetic acid-mediated diketopiperazine formation followed by N-benzylation proceeded smoothly to provide cyclodipeptide 17 on decagram scale. Conversion of 17 under our reaction conditions previously developed for the synthesis of mycocyclosin proved viable and robust to result in the formation of the desired cyclophane 18 in 81% yield on gramscale. Subsequent selective debenzylation of the phenolic ether 18

proceeded quantitatively with BCl3 and pentamethylbenzene at -78 ºC to give rise to diketopiperazine 19 as the desired oxidative dearomatization precursor. Hypervalent iodine-mediated dearomatization reactions of phenols are known to proceed upon addition of nucleophiles in the para- and ortho-position of the aromatic moiety.18 However, when diketopiperazine 19 was subjected to diacetoxyiodobenzene in methanol at -6 ºC, the exclusive formation of ortho-adduct 20 was observed, presumably as a result of the strained and congested nature of the cyclophane system. We next investigated protocols to effect selective conjugate reduction of quinone 20.19 Morrow and Doty previously reported an efficient procedure for the conjugate reduction of cyclic enones,20 relying on the bulky Lewis acid MAD21 to complex the carbonyl to prevent 1,2-addition and L-selectride as a sterically demanding hydride source to favor 1,4-addition. Interestingly, 1,4-reduction of quinone 20 relying on L-selectride proceeded selectively to form methoxy ketone 21 in 79% yield without evidence for competing 1,2-addition, which is most likely also a result of the strained nature of the macrocyclic system. Although 21 incorporates the desired ,-enone regiochemistry found in herqulines A-C (1-3), we were then faced with the challenge of selectively reducing the methoxy moiety. Procedures relying on SmI2 seemed most promising as 2-methoxy-substituted cyclohexanones have been reported to undergo efficient reduction via intermediate samarium-enolates and asymmetric variants of this transformation using chiral proton sources have been developed.22 When diketopiperazine 21 was converted with 2.2 equivalents of SmI2 under conditions originally reported by Mikami,22b the selective formation of a new product was observed as a single stereoisomer in 77% yield and the structure of the desired ,-enone 22 was confirmed upon X-ray analysis. Our subsequent investigations revealed that adjusting the diketopiperazine oxidation state prior to reductive dearomatization of the remaining aromatic system proved beneficial. However, only limited examples for piperazine formation from diketopiper

Figure 3. A. Literature precedent for the formation of ,-enone 9 in Birch reductions of L-tyrosine. B. Birch reduction of biaryl 10 results in formation of undesired ,-enone regioisomer 13. azines exist,23 and the application


Page 2 of 6

Page 3 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society

Figure 4. Synthetic strategy towards herqulines B (2) and C (3) relying on protected mycocyclosin derivative 18 as key synthetic intermediate. of those reported (e.g. LiAlH47b, BH3·THF23, Ni(II)/PhSiH324) resulted in only limited quantities of piperazine 23 or decomposition. Ultimately, we found reaction conditions adapted from an iron-catalyzed amide reduction protocol developed by Beller25 relying on disilanes as reductants to be superior, resulting in 60% yield of the

Figure 5. A. Birch reductions of ketone 23 result in overreduction while acetal 25 proves unreactive. B. Literature precedent for intramolecular H-transfer in Birch reductions.

desired piperazine 23, the formation of which was subsequently confirmed by X-ray analysis. We anticipate these reaction conditions to be general for the selective reduction of complex diketopiperazines. With a viable route to ,-enone 23 secured, we investigated reaction conditions for efficient dearomatization of the remaining aromatic ring. To our surprise, Birch reduction of enone 23 did not result in dearomatization but instead favored the formation of alcohol 24 in 20% yield together with a complex mixture of overreduction products (Fig. 5A). Based on these results, we postulated that protection of the ketone moiety was required in the Birch reduction to ensure a selective transformation. However, acetal 25 proved unreactive under various Birch reduction conditions (extended reaction times, increased metal equivalents, various proton sources) and the starting material was reisolated exclusively. These results were in stark contrast to those observed with ketone 23 which had proven exceptionally reactive under Birch reduction conditions. Based on these observations, we hypothesized that reduction of the ketone moiety to the corresponding alcohol not only precedes but facilitates subsequent dearomatization of the aryl subunit. Literature precedent by Paddon-Row on the effect of proximate hydroxy-groups to act as efficient intramolecular proton sources in Birch reductions26 further corroborated our hypothesis. Specifically, syn-methoxy anthracene 27 slowly resulted in the formation of skipped diene 29 as the anticipated Birch reduction product, while the reaction of the corresponding syn-alcohol 28 was not only observed to proceed significantly more rapid but also resulted in the exclusive formation of alkene 30 as a distinct product. Intrigued by this report, we decided to reduce ,-enone 23 to the corresponding alcohol to gain experimental support for our hypothesis with the ultimate goal of developing a selective protocol for the final dearomatization towards herqulines A-C (1-3). Reduction of 23 relying on NaBH4 proceeded selectively to provide alcohol 24 as a single stereoisomer in 80% yield (Fig. 6). Subsequent conversion of 24 under Birch reduction conditions proceeded smoothly to exclusively form skipped diene 31 in 55% yield.



Figure 6. Completion of the syntheses of herquline B (2) and herquline C (3). Aqueous acidic hydrolysis of methyl enol ether 31 afforded the desired ,-enone 32 in 90% yield. Completing the synthesis of herquline C (3) required oxidation of the secondary alcohol in 32 which proceeded readily under Swern oxidation conditions in 82% yield. Subjection of the resulting 1,4-diketone 33 to standard hydrogenolysis conditions with Pd/C resulted in the formation of herquline C (3) in 95% yield. Epimerization of 1,4-diketone 33 relying on superstoichiometric amounts of DBU4b formed stereoisomer 34 in 97% yield, which upon hydrogenolysis gave rise to herquline B (2) in 90% yield. In conclusion, we report herein the total syntheses of herqulines B (2) and C (3) from a derivative of the cyclodipeptide mycocyclosin. Our strategy builds on pioneering work of Hutton and coworkers who demonstrated that a Pd-catalyzed Suzuki-Miyaura cross-coupling could overcome the inherent strain of these compounds to assemble the biaryl subunit. Work from our own laboratories identified reaction conditions to provide these cyclophanes on scale which ultimately enabled synthetic studies towards the herqulines A-C (1-3). Our synthetic efforts demonstrated that a consecutive reduction strategy relying on a hypervalent iodine-mediated dearomatization, diketopiperazine reduction, followed by a final Birch reduction facilitated via an intramolecular proton source are efficient in adjusting the mycocyclosin oxidation state and complete the syntheses of herqulines B (2) and C (3).

The Supporting Information is available free of charge on the ACS Publications website. Experimental procedures and spectral data; (PDF) X-ray crystallographic data for 13 (CIF) X-ray crystallographic data for 22 (CIF) X-ray crystallographic data for 23 (CIF) X-ray crystallographic data for 24·HCl (CIF)

* [email protected]

‡These authors contributed equally.

This work was supported by the Alfred P. Sloan Foundation, the David and Lucile Packard Foundation, and the Camille and Henry Dreyfus Foundation (fellowships to C.S.S.). C.C.M. thanks the National Science Foundation for a predoctoral fellowship. We are grateful to Dr. Jeff Kempff for X-ray crystallographic analysis and Professor Corey R. J. Stephenson for helpful discussions.

(1) a) Ōmura, S.; Hirano, A.; Iwai, Y.; Masuma, R. Herquline A New Alkaloid Produced by Penicillium Herquei. J. Antibiot. 1979, 786; b) Furusaki, A.; Matsumoto, T.; Ogura, H.; Takayanagi, H.; Hirano, A.; Ōmura, S. X-Ray Crystal Structure of Herquline, a New Biologically Active Piperazine from Penicillium herquei Fg-372. J. Chem. Soc. Chem. Comm. 1980, 698. (2) Chiba, T.; Asami, Y.; Suga, T.; Watanabe, Y.; Nagai, T.; Momose, F.; Nonaka, K.; Iwatsuki, M.; Yamada, H.; Ōmura, S.; Shiomi, K. Herquline A, produced by Penicillium herquei FKI-7215, exhibits anti-influenza virus properties. Biosci. Biotechnol. Biochem. 2017, 81, 59. (3) Enomoto, Y.; Shiomi, K.; Hayashi, M.; Masuma, R.; Kawakubo, T.; Tomosawa, K.; Iwai, Y.; Ōmura, S. Herquline B, a Platelet Aggregation Inhibitor Produced by Penicillium herquei Fg-372. J. Antibiot. 1996, 50. (4) a) Cox, J.B.; Kimishima, A.; Wood, J.L. Total Synthesis of Herquline B and C. J. Am. Chem. Soc. 2018, 141, 25; b) He, C.; Stratton, T.P.; Baran, P.S. Concise Total Synthesis of Herqulines B and C. J. Am. Chem. Soc. 2018, 141, 29. (5) Yu, X.; Liu, F.; Zou, Y.; Tang, M.-C.; Hang, L.; Houk, K.N.; Tang, Y. Biosynthesis of Strained Piperazine Alkaloids: Uncovering the Concise Pathway of Herquline A. J. Am. Chem. Soc. 2016, 138, 13529. (6) a) Hoffmann, R. W. Elements of Synthetic Planning, Springer-Verlag, Berling Heidelberg, 2009; b) DeMartino, M.P.; Chen, K.; Baran, P.S. Intermolecular Enolate Heterocoupling: Scope, Mechanism, and Application. J. Am. Chem. Soc. 2008, 130, 11546. (7) Several Ph.D. theses describe synthetic efforts towards the herqulines, see: a) Kim, G.T. Ph.D. Thesis, Korea Advanced Institute of Science and Technology, November 1997; b) Hart, J.M. Ph.D. Thesis, University of Leeds, June 2004; c) Stawski, P.S. Ph.D. Thesis, Ludwigs-MaximiliansUniversität München, December 2012; d) Yang, H. Ph.D. Thesis, University of Birmingham, August 2015. (8) Belin, P.; Le Du, M.H.; Fielding, A.; Lequin, O.; Jacquet, M.; Charbonnier, J.-B.; Lecoq, A.; Thai, R.; Courҫon, M.; Masson, C.; Dugave, C.; Genet, R.; Pernodet, J.-L.; Gondry, M. Identification and structural basis


Page 4 of 6

Page 5 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 2009, 106, 7426. (9) a) Fonvielle, M.; Le Du, M.H.; Lequin, O.; Lecoq, A.; Jacquet, M.; Thai, R.; Dubois, S.; Grach, G.; Gondry, M.; Belin, P. Substrate and Reaction Specificity of Mycobacterium tuberculosis Cytochrome P450 CYP121. Insights from Biochemical Studies and Crystal Structures. J. Biol. Chem. 2013, 288, 17347; b) Dornevil, K.; Davis, I.; Fielding, A.J.; Terrell, J.R.; Ma, L.; Liu, A. Cross-linking of dicyclotyrosine by the cytochrome P450 enzyme CYP121 from Mycobacterium tuberculosis proceeds through a catalytic shunt pathway. J. Biol. Chem. 2017, 292, 13645. (10) Houk and Tang showed that despite the close structural resemblance between mycocyclosin and the herqulines, their biosynthetic pathways are distinct. While mycocyclosin is biosynthetically derived from an oxidative biaryl coupling reaction of a diketopiperazine derived from L-tyrosine, the herqulines are formed in an analogous biaryl coupling reaction of a piperazine precursor. See ref. 5 for details. (11) Cochrane, J.R.; White, J.M.; Wille, U.; Hutton, C.A. Total Synthesis of Mycocyclosin. Org. Lett. 2012, 14, 2402. (12) Zhu, X.; McAtee, C.C.; Schindler, C.S. Scalable Synthesis of Mycocyclosin. Org. Lett. 2018, 20, 2862. (13) Adamo, C.; Amatore, C.; Ciofini, I.; Jutand, A; Lakmini, H. Mechanism of the Palladium-Catalyzed Homocoupling of Arylboronic Acids: Key Involvement of a Palladium Peroxo Complex. J. Am. Chem. Soc. 2006, 128, 6829. (14) Laguzza, B.C.; Ganem, B. A New Protecting Group for Amines. Synthesis of Anticapsin from L-Tyrosine. Tetrahedron Lett. 1981, 22, 1483. (15) Rabideau, P.W.; Marcinow, Z. The Birch Reduction of Aromatic Compounds. Org. React. 1992, 42, 1. (16) Biaryl systems have been shown to undergo double, consecutive Birch reductions. Birch, A.J.; Nadamuni, G. Reduction by Dissolving Metals. Part XX. Some Biphenyl Derivatives. J. Chem. Soc. Perkin Trans. I, 1974, 0, 545. (17) For a discussion of the use of hypervalent iodine reagents for dearomatizations in the context of herquline intermediates, see ref. 7b, pp 126-129. A hypervalent iodine-mediated biaryl reduction was also used in the approach of Wood and coworkers towards herqulines B (2) and C(3). (18) For examples of hypervalent iodine-mediated reductions of tyrosine derivatives, see: a) Rama Rao, A.V.; Gurjar, M.K.; Sharma, P.A. Studies directed towards the total synthesis of aranorosin. Tetrahedron Lett. 1991, 32, 6613; b) Wipf, P.; Kim, Y. Studies on the synthesis of Stemona Alkaloids; stereoselective preparation of the hydroindole ring system by oxidative cyclization of tyrosine. Tetrahedron Lett. 1992, 33, 5477; c) Hara, H.; Inoue, T.; Nakamura, H.; Endoh, M.; Hoshino, O. A Novel Feature in Phenyliodine Diacetate Oxidation. Tetrahedron Lett. 1992, 33, 6491; d) McKillop, A.; McLaren, L.; Watson, R.J.; Taylor, R.J.K.; Lewis, N. A Concise Synthesis of the Novel Antibiotic Aranorosin. Tetrahedron Lett. 1993, 34, 5519; e) Karam, O.; Martin, A.; Jouannetaud, M.-P.; Jacquesy, J.-C. Synthesis of Hydroindolenones and Hydroquinolenones by Hypervalent Iodine Oxidation of Mono or Bicyclic Phenols. Tetrahedron Lett. 1999, 40, 4183; f) Ley, S.V.; Thomas, A.W.; Finch, H. Polymer-supported hypervalent iodine reagents in ‘clean’ organic synthesis with potential applications in combinatorial chemistry. J. Chem. Soc. Perkin Trans. I, 1999, 0, 669. (19) For a discussion of the use of L-selectride in conjugate reductions in the context of herquline intermediates, see ref. 7b, p. 130. (20) Doty, B.J.; Morrow, G.W. Conjugate reduction of quinone derivatives. A route to phenol keto-tautomer equivalents. Tetrahedron Lett. 1990, 31, 6125. (21) Ooi, T.; Maruoka, K. Exceptionally Bulky Lewis Acidic Reagent, MAD. J. Syn. Org. Chem. Jpn. 1996, 54, 200. (22) For examples of SmI2-mediated reductive enolizations of -heteroatom substituted ketones, see: a) Nakamura, Y.; Takeuchi, S.; Ohgo, Y.; Yamaoka, M.; Yoshida, A.; Mikami, K. SmI2-Mediated Reductive Enolization of -Hetero-Substituted Ketones and Enantioselective Protonation. Tetrahedron Lett. 1997, 38, 2709; b) Mikami, K.; Yamaoka, M.; Yoshida, A.; Nakamura, Y.; Takeuchi, S.; Ohgo, Y. Conformational Control in Proton Sources for Enantioselective Protonation of Samarium Enolate Derived from α-Methoxy-Substituted Ketones. Synlett 1998, 607; c) Nakamura, Y.; Takeuchi, S.; Ohgo, Y.; Yamaoka, M.; Yoshida, A.; Mikami, K. Enantioselective Protonation of Samarium Enolates Derived from -Heterosubstituted Ketones and Lactone by SmI2-Mediated Reduction. Tetrahedron 1999, 55, 4595; d) Nakamura, Y.; Takeuchi, S.; Ohgo, Y.; Curran, D.P. Preparation of a Fluorous Chiral BINOL Derivative and Application to an Asymmetric Protonation Reaction. Tetrahedron 2000, 56, 351; e) Misske, A.M.; Hoffmann, H.M.R. High Stereochemical Diversity and Applications

for the Synthesis of Marine Natural Products: A Library of Carbohydrate Mimics and Polyketide Segments. Chem. Eur. J. 2000, 6, 3313. (23) Jung, M.E.; Rohloff, J.C. Organic chemistry of L-tyrosine. 1. General synthesis of chiral piperazines from amino acids. J. Org. Chem. 1985, 50, 4909. (24) Simmons, B.J.; Hoffmann, M.; Hwang, J.; Jackl, M.K.; Garg, N.K. Nickel-Catalyzed Reduction of Secondary and Tertiary Amides. Org. Lett. 2017, 19, 1910. (25) Zhou, S.; Junge, K.; Addis, D.; Das, S.; Beller, M. A Convenient and General Iron-Catalyzed Reduction of Amides to Amines. Angew. Chem. Int. Ed. 2009, 48, 9507. (26) Cotsaris, E.; Paddon-Row, M.N. Remarkable Effects of Remotely Connected but Spatially Proximate Hydroxy-groups on the Birch Reduction of o-Xylene Moieties. J. Chem. Soc. Chem. Commun. 1982, 0, 1206.




Page 6 of 6

Bioinspired Syntheses of Herqulines B and C from Cyclodipeptide

Recommend Documents