Synthesis of the C4–C17 Fragment of Saliniketals A and B

Abstract

A highly stereoselective synthesis of the C4–C17 fragment of saliniketals A and B was completed. The key steps in this synthesis included a syn‐aldol reaction mediated by a boron enolate and a double diastereodifferentiating aldol reaction mediated by a titanium enolate. Moreover, a substrate‐controlled Grignard reaction, an intramolecular Wacker‐type cyclization and a Seyferth–Gilbert homologation provided the C4–C17 fragment of saliniketals A and B in 16 steps and with a 7 % overall yield.

Total Synthesis of the Oxopolyene Macrolide (−)-Marinisporolide C

“…An aldol reaction between 15 and the known aldehyde 16 (90%, dr > 95:05), followed by a reduction with Et 2 BOMe and LiBH 4 (99%, dr > 95:05), and a protection with 2,2-DMP gave compound 17 in 87% yield (Scheme ). Compound 17 was next transformed into sulfone 9 by removal of the C23 TBS group with TBAF (99%), Mitsunobu reaction of the resulting primary alcohol with 1-phenyl-1 H -tetrazole-5-thiol (PTSH), and oxidation with (NH 4 ) 6 Mo 7 O 24 ·4H 2 O and H 2 O 2 of the resulting sulfide . Overall, the C23–C35 sulfone 9 (more than 1.5 g prepared) was obtained in 13 steps and 18% yield from alcohol 10…”

Total Synthesis of (−)-Marinisporolide C

“…The synthesis of C1–C8 fragment proceeded uneventfully and phosphonates 6a and 6b were obtained in good yields from removal of silicon ether of compounds 71a and 71b , followed by treatment with PBr 3 and pyridine, and finally a Michaelis–Arbuzov reaction (Scheme ).…”

“…Incorporation of the phenyltetrazole sulfone moiety at C23 terminus of the compound 40 was executed by a three-step procedure (Scheme ). Removal of TBS ether of compound 40 (TBAF, THF, 99%) provided the primary alcohol 41 which was subjected to a Mitsunobu reaction to deliver sulfide 43 in 87% yield . Finally, oxidation of compound 43 (H 2 O 2 , (NH 4 ) 6 Mo 7 O 24 .4H 2 O, EtOH, 92%) gave the sulfone 10 , which corresponds to the C23–C35 fragment of marinisporolides …”

Studies towards the Synthesis of Aldgamycin – M

“…The compound 14 was subjected to desilylation by using TBAF in THF to afford the required primary alcohol 15 in 87% yield. Compound 15 was subjected to oxidation using Dess‐Martin periodinane and NaHCO 3 in dichloromethane to furnish the aldehyde, which was subjected to Grignard reaction by using 3‐butenylmagnesium bromide to obtain the diastereomeric compound 16 in 70% (over two steps), with 8:2 dr. The two diastereomers were separable in column chromatography.…”