Deoxy Sugars - ACS Publications

3 Deoxycyclitols: Stereochemical and NMR Studies G. E. M c C A S L A N D , M. O. N A U M A N N , and S T A N L E Y F U R U T A

Downloaded by UNIV LAVAL on July 14, 2016 | http://pubs.acs.org Publication Date: June 1, 1968 | doi: 10.1021/ba-1968-0074.ch003

University of San Francisco, San Francisco, Calif.

The deoxyinositols (quercitols, cyclohexanepentols) are useful model compounds which display many of the physical and chemical properties of true deoxy sugars. Although (+)-proto-quercitol, the best known isomer, was isolated from nature 118 years ago, no synthesis has been reported up until now. The synthesis here described is actually that of the (-)-enantiomer, starting with (-)-inositol; however, identical procedures applied to the readily available (+) or DL-inositol would give (+) or DL-proto-quercitol, respectively. The natural occurence of (—)-proto-quercitol has also been reported recently. Configurational interpretation of the NMR spectra of quercitols was at first difficult or impossible. Such interpretations can now easily be accomplished by recording the proton spectra at 220 MHz. (51.7 kilogauss), using a superconducting solenoid. The synthesis of ring-deoxy sugars (pseudo-hexoses) is also discussed.

T Tydroxylated cyclohexanes, especially those with five hydroxyl groups, are valuable model compounds which exhibit much of the stereochemical and physical behavior of true sugars and deoxy sugars, without complications attributed to ring-opening and closing, or anomerization. They may be important, also, because of their relationship to mt/o-inositol (2) which is present i n every living cell of every plant or animal, so far as is known, and is one of the very small group of organic compounds essential for growth of isolated human cells i n cultures (21,37). The cyclohexanediols, -triols, and -tetrols each have three structures (e.g,. 1,2; 1,3; and 1,4 for the diols), but the cyclohexanepentols and -hexols and cyclohexanol itself each have only one structure. F o r these twelve structures a total of fifty diastereomeric forms (28 meso, 22 racemic) is possible. Cyclohexanol and the -diols have long been known, 41 Hanessian; Deoxy Sugars Advances in Chemistry; American Chemical Society: Washington, DC, 1968.


42

DEOXY SUGARS

and the last of the -triols (29,30), -pentols (23,32), and -hexols (4) have recently been reported. A l l but two of the numerous -tetrol diastereomers have been reported, and work on these two remaining isomers is i n progress (27). The large number of meso diastereomers (28 out of 50) is an interesting feature of these cyclitols; it results from the symmetry of the cyclohexane ring, which is not present i n the hexopyranose ring. Although the best alicyclic analogs of deoxyhexoses might be the deoxyinososes—e.g. 1, very little is yet known about these compounds. The present chapter w i l l therefore be devoted mainly to the deoxyinositols (quercitols, cyclohexanepentols), which strictly speaking are analogs of deoxyhexitols. A section is also included on the new ring-deoxy or "pseudo" sugars—e.g. 34, i n which the pyranose ring-oxygen atom is replaced by methylene. These compounds have the primary alcohol sidechain typical of hexopyranoses. Monodeoxyinositols

or

Quercitols

Since earlier reviews (20,21,37) are available, only very recent developments w i l l be considered here. Synthesis of Deoxyinosamines from vibo-Quercitol. As yet, the quercitols have rarely been used as synthetic starting materials. Recently, however, Suami and Yabe (42) have reported clever syntheses of two (acetylated) deoxyinosamines (8 and 9, Y = N H A c ) and one (acetylated) deoxyinosadiamine (10, Y = N H A c ) from racemic uifco-quercitol (4) . The syntheses were effected by selective mesylation of one or two hydroxyl groups and displacement of each mesyloxy group by an azido group, which was reduced to amino. Although attempted S 2 displacement of cyclohexane substituents is often unsuccessful, the powerfully nucleophilic azide ion is usually able to displace an alkylsulfonoxy group, and this route has been exploited i n several recent cyclitol syntheses. The vibo or D L (124/35) quercitol (4) needed for the synthesis was prepared from mt/o-inositol (2) via the bromoquercitol (3) according to the method of McCasland and Horswill, (28). B y acetonation, acetylation, deacetonation, and equatorial mesylation the mesyloxy derivative (5) was obtained. This was converted to the azidotetrol derivative (8) ( Y = N ) ; the anchimeric effect of the position 3 acetoxy group (formula 5) resulted i n inversions of configuration at positions 2 and 3. The proto or D L (134/25) configuration was retained i n the final product, 8 ( Y = N H A c ) , a derivative of 3-amino-l,2,4,5-cyclohexanetetrol (42). The 1-mesyloxy intermediate (6) was similarly prepared via the equatorial monobenzoate, and it reacted with azide ion by a single S 2 displacement, since no anchimeric effect was possible here. The scyllo N

8

N

Hanessian; Deoxy Sugars Advances in Chemistry; American Chemical Society: Washington, DC, 1968.

MCCASLAND

ET

AL.

Deoxycyclitols


3.

CHART A


43

44

DEOXY SUGARS


or D L (135/24) configuration was retained i n the final product, 9 ( Y = N H A c ) , a derivative of 5-amino-l,2,3,4-cyclohexanetetrol (42). Finally the dimesyl derivative (7) was prepared i n a similar manner. W h e n it reacted with azide ion, configurational inversions were observed at positions 1, 2, and 3 (formula 7), owing i n part to the anchimeric effect of the position 3 acetoxy group. The vibo or D L (145/23) configuration (same as i n the starting material) was retained i n the final product 10 ( Y = N H A c ) , a derivative of 3,5-diamino-l,2,4-cyclohexanetriol (42). A l l of the intermediates and products were characterized by N M R (42). Natural Occurrence of (-)-proto-Quercitol. Although the dextrorotatory form (12) of proto-quercitol was discovered in acorns more than a century ago by Braconnot (5), who at first thought that it was lactose, the levorotatory form (13) remained unknown until 1961. In that year, Plouvier isolated it from leaves of the tree Eucalyptus populnea; the yield was 0.55% (36). The optical rotation of the new compound was equal and opposite to that of the dextro enantiomer, and it was identical to the latter i n its crystal form, melting point, solubilities, molecular formula and infrared spectrum. Plouvier then prepared the previously unknown racemic form of proto-quercitol by mixing equal weights of the two enantiomers. The melting point (237°C.) of the mixture was not depressed, and its (presumably solid state) infrared spectrum reportedly (36) was identical with that of either active form. It thus appears that DL-profo-quercitol exists as a solid solution, not a racemic compound or conglomerate. The discoverer of levorotatory profo-quercitol unfortunately described it (36) as "L-quercitol." The capital letter V should of course be understood to designate configuration, not rotation. A n d according to one widely accepted convention (18,19), the quercitol stereosiomer which has the configuration 13 would be designated V , not " L " . (See formulas 12 and 13.) The name quercitol is now used i n a generic sense (cyclohexanepentol), so that there are actually six diastereomers to which the name "L-quercitol" might apply. According to the modified Maquenne system (18,19,31) used i n this chapter, the diastereomeric configuration of any cyclitol is expressed by a fraction, and position-numbering, if otherwise equivocal, is so assigned that the numerator w i l l have the lowest possible numbers. For example, proto-quercitol (12 or 13) is designated (134/25,), not (14/ 235) or (25/134). To specify enantiomeric configuration, the pre-numbered perspective formula is so oriented i n three dimensions that its numbering w i l l proceed from right to left around the front of the ring, as customary for


3.

45

Deoxycyclitols

MCCASLAND ET A L .

HO HO

OH

OH HO

OH 3

HO

\

|*

(-) —VIBO-QUERCITOL L (124/35)

(-) —PROTO-QUERCITOL

( + )—PROTO-QUERCITOL

D

(* /25) 34

L (134/25)

11 Downloaded by UNIV LAVAL on July 14, 2016 | http://pubs.acs.org Publication Date: June 1, 1968 | doi: 10.1021/ba-1968-0074.ch003

2

13

12

R —o 5

R —O

OH

HO

OMe

fi

MeO

OH

5

20

16 R = CO

Deoxy Sugars - ACS Publications

Recommend Documents