| Summary: | 碩士 === 國立中興大學 === 化學系所 === 101 === For construction of the six-membered framework of (-)-Oseltamivir (Tamiflu), we envisioned using Lewis acid-promoted coupling of chiral acetal-aldehyde 95 with ethyl silylmethylcrotonates 94 and 156. We postulated that 95 could be attained from L-serine via acid-promoted esterification, N-acetylation, silylation of hydroxyl group with TBS-Cl, reduction of ester, benzylation of hydroxyl group, removal of silyl group, TEMPO-mediated oxidation of primary alcohol to aldehyde, acetalization of formyl group with 3-pentanol, deprotecting benzyl ether, and TEMPO-mediated oxidation of primary alcohol to aldehyde. On the other hand, chiral acetal-aldehyde 95 could also be attained from L-tartaric acid via acid-promoted esterification and cyclosulfonation of 1,2-diol with SOCl2, introduction of the azido group by SN2 chemistry, controlled reduction of ester, NaIO4-promoted oxidative cleavage of 1,2-diol, hydrogenation of azido group, N-acetylation, and acetalization of formyl group with 3-pentanol. With chiral acetal-aldehyde 95 in hand, attention was directed toward constrction of ethyl silylmethylcrotonates 94 and 156. We envisioned 94 and 156 could be synthesized from 2-methyl-2-propenol 97 via C-silation with TMS-Cl, PCC-mediated oxidation of primary alcohol to aldehyde, CuCl2 ‧ 2H2O, tBuOOH-mediated oxidation of aldehyde to acid, and esterification. For construction of the six-membered framework of (-)-Oseltamivir (Tamiflu), we also envisioned 1,4-addtion of nitroacetamide 120 with bromosilane 125. We postulated that bromosilane 125 could be attained from propargyl alcohol via O-and C-silation, and bromonation of allylsilane. On the other hand, nitoacetamide 120 could be attained from acrolein via acetalization of formyl group with 3-pentanol, ozonolysis, base-mediated nitro-aldol reation between nitromethane and aldehyde, O-mesylation, introduction of amino group by SN2 chemistry, and N-acetylation.
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