Epimers hydrogenolysis

The same basic strategy was applied to the synthesis of the smaller fragment benzyl ester 28 as well (Scheme 4). In this case, aldehyde 22 prepared from (S)-2-hydroxypentanoic acid [9] was allylated with ent-10 and tin(IV) chloride, and the resulting alcohol 23 was converted to epimer 24 via Mitsunobu inversion prior to phenylselenenyl-induced tetrahydrofuran formation. Reductive cleavage of the phenylselanyl group, hydrogenolysis of the benzyl ether, oxidation, carboxylate benzylation, and desilylation then furnished ester 28. 

FNA was synthesized by reaction of /(-naltrexamine (48) with the monomethyl ester of fumaroyl chloride [79], Amine (48) was prepared first from naltrexone by reductive amination with sodium cyanoborohydride in the presence of ammonium acetate to give 6a- and 6/i-epimers (ratio ca. 2 1). Separation was achieved by fractional crystallization [83], An improved synthesis of (48) was reported via the dibenzyliminium salt of naltrexone (46 easily accessible from naltrexone and dibenzylamine) which was reduced with sodium cyanoborohydride to give exclusively the 6/i-epi-mer (47). Catalytic hydrogenolysis afforded /i-naltrexamine (Scheme 3.6) [84]. 

Two further quaternary pyrrolizidine alkaloids have been isolated by Sasaki and Hirata from Anodendron affine Druce. These are anodendrine (26) and its C-1 epimer alloanodendrine. In confirmation of these structures, anodendrine gave (+ )-laburninic acid (27) on palladium-catalysed hydrogenolysis, whereas alloanodendrine gave (-t-)-isoretronecanolic acid, the C-1 epimer of (27). The structures of both zwitterionic alkaloids were then finally established by synthesis. 

The two diastereoisomers were separated after conversion of the corresponding tosylates to the azide 23 and its epimer. Next, 23 was converted to A-methylcarbamate 24 by hydrogenolysis in the presence of Boc20 [19] and then methylation [20], Reduction of the ester in 24 with... 

Several steps are required to convert D-mannose (244) into compound (245) from which, by phosphorylation with diphenyl phosphorochloridate and triethylamine, followed by hydrogenolysis, (246) may be obtained. Attempts to modify this latter substance at C(l) so as to introduce a further phosphorus-containing function have not been. successful. The bis(isopropylidene) derivative (247) reacted with tetraethyl methylenebisphosphonate to give (248), together with its C(l) epimer and (249). Treatment of the anomers of (248) with p-toluenesulphonic acid in acetone so as to remove the 4,6-isopropylidene group, and further phosphorylation (same reagents). 

The chemistry of catharanthine is still being vigorously investigated, in connection with the synthesis of vinblastine and its analogues. Details of some of the earlier work have now become available." New work includes the preparation" of a potentially useful keto-ester (220) from an isoxazolidine derivative (219) obtainable from catharanthine. Hydrogenolysis of (219), followed by allylic oxidation and internal Michael addition, affords (220) as a mixture of C-20 epimers (Scheme 38). Other derivatives include" 15jS-hydroxy-15,20-dihydro-... 

Stereospecific generation of natural C-17 stereochemistry and the natural and unnatural C-20 epimers of steroids was achieved by Pd-catalyzed hydrogenolysis of C-17 and ( )- and (Z)-C-20 jS-aUyUc carbonates, which are readily available from the keto steroids. (Scheme 9). 

An extended NeuAc analogue 49 has been prepared by the reaction of 5,6-0-isopropylidene-A-acetylmannosamine with disodium acetone dicarboxylate in the presence of nickel acetate the C-5 and C-6 epimers of 49 were also formed. Deprotection of 49 by hydrogenolysis gave the free acid which decarboxylated readily. 9 Treatment of the Wittig product 50 under Wacker-type conditions led to the glycoside 51 of a 3-ulosonic acid (Scheme 7). ... 

Deoxy-N-acetylneuraminic acid (5) was prepared by hydrogenation of a 2-ene,6 whilst the epimer at C-2 was the major product formed by hydrogenolysis of the corresponding P-D-glycosyl chloride.6 Neither (5) nor its epimer was an inhibitor of CMP-sialate synthetase, in contrast to the... 

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