With osmium synthesis

Many of the reactions already discussed for the preparation of bis-oxygenated pregnanes can also be used for the synthesis of 17,20,21-tris-oxygenated pregnanes by proper choice of substrate. Thus, reaction of a 17-vinyl-17-hydroxy steroid or a A -21-hydroxypregnene with osmium tetroxide will give the 17,20,21-triol, and the Stork reaction can be applied to 17a-hydroxy-20-keto steroids. 

The total synthesis of ( )-geissoschizine (30) was reported by Yamada et al. (156) in 1974. The geometrically pure p-nitrophenyl ester 272 was condensed with tryptamine, and then the resulting amide 273 was transformed to lactam aldehyde 274 by hydroxylation with osmium tetroxide, metaperiodate oxidation, and Pictet-Spengler cyclization. 

For a synthesis of leurosidine (56), 15,20-dihydrocatharanthine iV-oxide (57) was subjected to coupling with vindoline (3) under the modified Polo-novski conditions. The initial adduct, imonium salt 58, was converted to the enamine 59 in base. Oxidation of this product with osmium tetrox-ide proceeded chemo- and stereoselectively, without reaction of the... 

The first useful asymmetric synthesis with a-halo boronic esters utilized (S)-pinanediol [1S-(la,2/1.3//,5a)]-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol as the chiral director39,40. This diol is easily prepared from ( + )-a-pinene by a catalytic hydroxylation with osmium tetroxide, and its enantiomer (i )-pinanediol is available from (-)-(a)-pinene41,42. Pinanediol esters remain useful in view of their excellent stability as well as the ease of preparation of the diol. and their stereoselectivity is very high even though it is no longer the state of the art. 

A base-catalyzed, elimination reaction was a key step in a synthesis of D-ribose from L-glutamic acid.188 In that work, L-glutamic acid was converted, by a series of reactions, into 5-0-benzyl-2,3-dideoxy-D-glycero-pentofuranose (157) from compound 157, a mixture of glycosides was obtained which, on treatment with bromine and calcium carbonate, gave the monobromo derivative 158 as a mixture of diastereoisomers. Base-catalyzed dehydrobromination of 158 afforded the unsaturated derivative 159. Hydroxylation of 159 with potassium permanganate or with osmium tetraoxide gave a mixture of methyl 5-0-benzyl-/3-D-ribofuranoside and methyl 5-O-benzyl-a-D-lyxofuranoside. 

The addition reaction to branched glycoenopyranosides sometimes offers a stereospecific pathway to A-type, branched sugars. A stereospecific synthesis of the e valose (15) derivative (110) by cis-hy droxy lation of methyl 4-0-benzoyl-2,3,6-trideoxy-3-C-methyl-a-D-en/thro-hex-2-en-opyranoside (109), derived from 57a (R = Me), with osmium tetraoxide... 

The rest of the synthesis (Scheme 13) is completely stereospecific and most of the steps are known (20). The bicyclic acid was oxidatively decarboxylated with lead tetraacetate and copper acetate (21). The resulting enone was alkylated with methyllithium giving a single crystalline allylic tertiary alcohol. This compound was cleaved with osmium tetroxide and sodium periodate. Inverse addition of the Wittig reagent effected methylenation in 85% yield. Finally, the acid was reduced with lithium aluminum hydride to grandisol. 

A stereospecific reduction of a pseudoglycal has been used to prepare the same isomer.23 Reduction of methyl 4,6-0-benzylidene-2,3-dideoxy-/3-D-erythro-hex-2-enopyranoside (6) with lithium aluminum deuteride led to the stereospecific synthesis of 4,6-0-benzylidene-3-deoxy-D-glucal-3(S)-d (7), which, after oxidation with osmium tetra-oxide-periodate followed by debenzylidenation, gave 2-deoxy-D-erythro-Tpentose-2(S)-d (2-deoxy-2-deuterio-D-arabinose) (8). Reduc-... 

Alternatively, synthesis of compound 215 (4-epimer of 208) started by initial inversion of the OH group at C-l of 207 (Scheme 27).35,96,99 101 Acid hydrolysis of 207 gave the triol 209 (100%), which was identified as its tetraacetate 210, whose allylic hydroxyl group was selectively sulfonylated with mesyl chloride to afford 211, which was then converted into the acetate 212 (65%). On treatment with an excess of sodium acetate in DMF, 212 afforded 213 (60%). Oxidation of 213 with osmium tetraoxide gave, after acetylation, 214 and 216. Furthermore, epoxidation of 213 gave a single spiro epoxide 214 (64%), which was transformed exclusively into 216 (83%)... 

Sharpless also introduced the catalytic asyimnetric dihydroxylation of cis-disubstituted olefins with osmium tetroxide. Jacobsen s catalyst, mentioned earlier, is also much used in synthesis. 

Synthesis of pregnane and corlieaid side chainsJ The l7 -ethynylcarbinol acetate (I) is reduced by zinc dust in refluxing diglyme, a process which is accompanied by rearrangement and elimination, to give the allenyl steroid (2) in 86% yield. The desired cortieoid side chain (3) can be formed from (2) by reaction with osmium tetroxide... 

Nonsymmetrical coupling reactions have been used extensively by Schafer and coworkers to generate a variety of natural products [1,8-10, 13-17]. A typical procedure calls for the use of a large excess (5-10 equivalents) of one of the acids. In conjunction with a total synthesis of the pheromone brevicomin [8] (21), compounds 24 and 25 (ratio of 5 1) were co-oxidized in methanolic potassium hydroxide to afford ketone 23 in 33% yield. The heterocoupling was complicated by the allylic nature of the radical derived from 24 the undesired coupling isomer constituted 12% of the product. Subsequent treatment of the desired isomer 23 with osmium tetroxide formed diol 22. Acid-catalyzed intramolecular ketalization led to brevicomin (21) in a 42% yield. 

---