TOTAL SYNTHESES OF (-)-PAPUAMINE AND (-)-HALICLONADIAMINE

The pentacyclic marine alkaloids (-)-papuamine (1) and (-)-haliclonadi amine (2) have been prepared by total synthesis. The synthesis began w ith (-)-8, which was converted into diester 20 by way of bis-mesylate 17, dinitrile 18, and diacid 19. Dieckmann cyclization of 20 provided keto ester 21, which was transformed into acetal 22. After hydrolysis of the acetal, ketone 25 was subjected to reductive amination with 1,3 -propanediamine and sodium triacetoxyborohydride to obtain diamines 26 and 27 as a 71:29 mixture of diastereomers, favoring the symmetrical isomer having the papuamine relative configuration. After transformati on of the diamines to their t-Boc derivatives, the benzyl ethers were cleaved and the resulting diol was oxidized to dialdehyde 30. Applicat ion of the Seyferth procedure for conversion of aldehydes to alkynes g ave a mixture of diynes 31 and 32. After removal of the t-Boc protecti ng groups from 31, diamino diyne 15 was treated with tributylstannane and azoisobutyronitrile to obtain the bis-vinylstannane 34. Treatment of this compound with Pd(II) and Cu(I) in the presence of air produced (-)-papuamine (1). (-)-Haliclonadiamine (2) was obtained from the uns ymmetrical isomer, 32. The NMR spectra of the synthetic alkaloids were identical to those of authentic samples of the natural alkaloids.