Branched-chain oxiranes

The racemic form of methyl 3,4-anhydro-/3-mycaroside (82) has been synthesized 35 it is an epoxide of a branched-chain sugar having the oxirane ring fused to the pyranose ring. Hydrolysis of the oxirane ring with hydrochloric acid in aqueous p-dioxane occurs with substitution at C-4, the (more accessible) secondary position, as would be expected from its favored °H, conformation (82) anticipated, because it is an analog of the 3,4-anhydro-D-allopyranoside derivatives considered previously (see p. 148). 

With the spiro-epoxides of branched-chain sugars, the oxirane protons appear somewhat farther upfield, between r 6.8 and 7.5, the two protons showing a variable difference in chemical shift.224,227... 

Epoxy sugars are frequently used as starting compounds in the synthesis of sugar derivatives (compare Section IV) such as halo, amino, azido, thio, deoxy, and branched-chain derivatives. The oxirane ring is in general more reactive than the oxetane or oxolane ring. It is opened with nucleophiles under base or acid catalysis. On the other hand, the oxirane ring remains unattacked under the conditions of catalytic debenzylation on palladium,... 

On the other hand, the situation is more complex with flexible oxirane derivatives. This is clearly demonstrated by comparison of the equilibrium mixtures resulting after epoxide migration of different types of anhydro hexoses,278,286,304 their 6-deoxy derivatives 175, 176,520 branched-chain hexoses 177, 178,520,521 and anhydro hex-2-uloses.304... 

J. Yoshimura, N. Kawauchi, T. Yasumori, K. Sato, and H. Hashimoto, Branched-chain sugars. 37. Synthesis of 2,3-anhydro-hexopyranosides and 3,4-anhydro-hexopyranosides having a methyl branch on the oxirane ring, and their reactions with some lithium methylcuprate reagents, Carbohydr. Res., 133 (1984) 255-274. 

The diol 59 was used for an ingenious synthesis of L-mycarose (62, 2,6-dideoxy-3-C-methyl-L-n bo-hexose) and olivomycose (63, 2,6-dideoxy-3-C-methyl-L-ara /no-hexose). The sequence of reactions consisted in 1 epoxidation of the double bond and separation of both stereoisomeric epoxides formed, 2° reduction of the oxirane ring to form two triols 60 and 61, and 3° ozonolytic degradation of the aromatic ring to a carboxyl group. Each trihydroxyacid was converted into a lactone and the lactones were eventually reduced to the required branched-chain sugars 62 and 63. 

Oxirans - The use of pyranose epoxides in the preparation of sugar amino acids and peptides, aminodeoxy, halodeoxy, branched-chain, cyclopropanated and aziridino sugars has been reviewed. ... 

The most common methods for the synthesis of branched-chain sugars involve the reduction of aUcyUdene glycosides, opening of the sugar oxiranes by carbon nucleophiles, and the additicm of organometallic reagents to glycopyranosiduloses [11]. 

The preferential reaction of benzylidene acetals in compounds also containing oxiran units is mentioned in Chapter 5. Other hydroxy branched-chain sugars are mentioned below as hydration products of unsaturated analogues. 

Step polymerization reactions, where little molecules such as epoxies (oxiranes) react with amines, or isocyanates react with polyols with functionality greater than two to form short, branched chains, eventually condensing it into epoxies or polyurethanes, respectively. Schematically... 

Oxirans.—A convenient synthesis of methyl 2,3-anhydro-)8-D-ribofuranoside is shown in Scheme Several oxirans of branched-chain sugars have been... 

Branched-Chain Alditols. - Reaction of sugar oxiran derivatives with excess of trimethylaluminium yield branched-chain deoxy-alditol derivatives, e.g.. (8)—>(9), in an unusual ring opening, chain extension process. The conversion of the benzyl glycoside (10) to... 

Oxirans derived from branched-chain sugars are mentioned in Chapter 4, while the m.s. of some 2,6-dideoxy-3-C-methylhexopyranose derivatives is referred to in Chapter 24. 

Lukac s group use D-galactose to prepare the branched-chain sugar (26), introducing the branch methyl groups using lithium dimethyl cuprate on oxiran intermediates, followed by 3-deoxygenation via the xanthate ester. 

The patterns of regio- and stereoselectivities become more complex in disubstituted oxiranes. Beginning with 2,2-disubstituted oxiranes, attack is always at the accessible C-atom. In terms of substrate enantioselectivity, it was found that 2-butyl-2-methyloxirane (2-methyl-1,2-epoxyhexane, 10.43, R = Bu) was hydrolyzed with a preference for the (5)-enantiomer. This substrate enantioselectivity was lost for branched analogues, namely 2-(/er/-bu-tyl)-2-methyloxirane (10.43, R = /-Bu) and 2-(2,2-dimethylpropyl)-2-meth-yloxirane (10.43, R = (CH3)3CCH2) [124], Thus, it appears that the introduction of a geminal Me group suppresses the enantioselectivity seen with branched monoalkyloxiranes, and reverses it for straight-chain alkyloxiranes. 

G. Bellucci, C. Chiappe, F. Marioni, M. Benetti, Regio- and Enantioselectivity of the Cytosolic Epoxide Hydrolase-Catalysed Hydrolysis of Racemic Monosubstituted Alkyloxiranes ,./. Chem. Soc., Perkin Trans. 1 1991, 361 - 363 G. Bellucci, C. Chiappe, L. Conti, F. Marioni, G. Pierini, Substrate Enantioselection in the Microsomal Epoxide Hydrolase Catalyzed Hydrolysis of Monosubstituted Oxiranes. Effects of Branching of Alkyl Chains ,./. Org. Chem. 1989, 54, 5978 - 5983. 

Synthesis of primidolol (65) can be carried out by a convergent scheme. One branch consists in application of the usual scheme to o-cresol (62) ring opening of the intermediate oxirane with ammonia leads to the primary amine (63). The side chain fragment (64) can be prepared by alkylation of pyrimidone (63) with ethylene dibromide to afford Alkylation of ami noalcohol with halide ... 

Exceptions to the generality of straight chains are FAs substituted with hydroxy, keto (0x0), and epoxy (oxirane) groups and FAs with unusual unsaturation. Methyl branched FAs occur mainly in bacteria, but also naturally in the fat of ruminant animals together with a series of odd-chain fatty acids. 

The next constitutional part of the side-chain FLCP structure (Fig. 4b) to include a chiral center would be the spacer. Scherowsky et al. succeeded in preparing FLCPs with a chirally branched spacer [69,70] and also with a spacer including an oxirane ring [71] ... 

Table 30 contains transition data on some compounds with terminal small rings (compounds 2 and 3). Compared with the simple alkyloxy group (compound 1), the small rings have an effect comparable to branched alkyls, but unlike that of five- or six-mem-bered rings. In order to obtain chiral materials, the introduction of an oxirane or thi-irane ring in the terminal chains is useful [143]. 

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