Higher-carbon sugars. Part 1. The synthesis of some octose sugars via the osmylation of unsaturated precursors

Abstract

The stereochemical outcome of the osmium tetraoxide oxidation of a number of unsaturated carbohydrate derivatives, including (€) -and (Z) -6,7-dideoxy-l,2 : 3,4-di-~-isopropylidene-a-o-ga/acto-oct-6-enopyranose (6) and (9), methyl (Z) -6,7 -dideoxy-1,2 : 3,4-di -0-isopropylidene-a-D-galacto-oct -6-enopyranuronate ( 8 ) , and 7,8-dideoxy-1,2 : 3,4-di-0-isopropylidene-a-D-glycero-~-ga/acto-oct-7 -enopyranose (1 0), has been examined. Such oxidations resulted in the preparation of the synthetically usef u I octose derivatives 1,2 : 3,4-d i -0 -isopropy l idene-x -D -erythro -D -ga/acto -octopyranose (1 8) and 1,2: 3,4: 6,7-tr~-~-~sopropyl~dene-~-~-erythro-~-ga/acto-octopyranose (31 ), as well as syntheses of Lthreo-D -ga/acto-octitol (1 4), D-erythro -D-ga/acto-octitol (21 ), L-erythro-o-galacto-octitoi (29), and D -threo -D-ga/aCtO-OCtitOI (35).The synthesis of sugars with carbon chains composed of more than six carbon atoms, the so-called higher-carbon sugars,' poses an interesting challenge.'-4 Such syntheses require the formation of carbon-carbon bonds and control of the stereochemistry at each newly created stereocentre. The concept of asymmetric synthesis was first realised with the Kiliani-Fischer cyanohydrin reaction, which was used to extend the aldose chain by one carbon atom from the reducing end.2*3 This procedure has been applied to most h e x o s e~,~.~ but, because of the asymmetric nature of the cyanohydrin synthesis, only a limited number of heptoses are available as substrates. In certain cases, syntheses were extended to give octose, nonose, and decose sugars, but the structures of many of these highercarbon sugars remain unproved.' In recent times, the cyanohydrin procedure has been augmented by other methods; ' theseO+ permit extension of the sugar chain by two or more carbon atoms in a single step, but seldom in a wholly predictable way, so that in spite of the long standing interest in higher-carbon sugars, only a handful of them containing eight or more carbon atoms are known.2 A resurgence of interest in the synthesis of higher-carbon sugars has followed the discovery of important antibiotics containing such higher-carbon sugars as the amino-octodioses (1) (from apramycin and oxyapramycin ') and the undecose hikosamine 8*9 (2) (from hikizimycin 9). Our interest in the synthesis of these and other higher-carbon sugars of biological interest prompted an examination of the oxidation of various unsaturated sugar derivatives with osmium tetraoxide. In choosing this approach we were influenced by the knowledge that the osmylation of allylic alcohols and ethers proceeds with moderate to marked stereoselectivity, which can be predicted on an empirical basis. l o Initially our efforts were directed towards the synthesis of octose sugars by extending the chain of the hexodialdose" (3) by two carbon atoms, as outlined in the Scheme. Unlike traditional methods, the carbon chain of the original hexose, in this instance D-galactose, is undergoing extension from the non-reducing end. This particular system...

Acyclic Stereocontrol Induced by Allylic Alkoxy Groups. Synthetic Applications of Stereoselective Dihydroxylation in Natural Product Synthesis

“…96 For example, in 1970 Szarek reported that treatment of olefin 83 with aqueous potassium permanganate gave diol 84 as the sole product.97 As shown in Table 7, entry 2, exclusive "anti" selectivity was obtained for catalytic osmylation. 47 There have appeared two additional comparison studies: both KMnC>4 and OSO4 dihydroxylations of olefin 85 (Table 11, entry 3) gave the anti diol in 3:1 selectivities. Similar results were obtained for olefin 86 (from Table 12, entry 5).…”

Selective synthesis and comparative activity of olefinic isomers of 1,2-benzothiazine-1,1-dioxide carboxylates as aldose reductase inhibitors

“…29 Anomalous Z selectivity depending on substrate and solvent is also reported. [30][31][32] The reaction of 1a and b 40 C proceeded with high Z stereoselectivity (76%; 2a : 3a ¼ 87 : 13) and (89%; 2b : 3b ¼ 83 : 17), respectively (Fig. 2).…”

Addition Reactions with Formation of Carbon–Oxygen Bonds: (iii) Glycol Forming Reactions

“…In the 2-halocyanoacetate procedure,2o a trans-bromohydrin (36; Scheme 3), prepared from an alkene, is esterified with cyanoacetic acid to give the 2-halocyanoacetate (37), and the latter is treated with sodium hydride to give, via the enolate anion, a cyanoketene acetal (38). Acid hydrolysis of the latter, followed by deesterification with base of the diol monocyanoacetate so-formed gives diol (39).…”