Studies on the synthesis of reidispongiolide A: stereoselective synthesis of the C(22)–C(36) fragment

Abstract

A highly stereoselective synthesis of the C(22)-C(36) fragment 2 of reidispongiolide A is described. This synthesis features the highly stereoselective mismatched double asymmetric crotylboration reaction of the aldehyde derived from 5 and the new chiral reagent (S)-(E)-7 that provides 12 with >15:1 d.r. Subsequent coupling of the derived vinyl iodide 3 with aldehyde 16 provided allylic alcohol 17, that was elaborated by three steps into the targeted reidispongiolide fragment 2.

Stereocontrolled Synthesis of a Cn–Cn+7Building Block (“Eastern Moiety”) for the Unnatural Enantiomers of Important Polyol,Polyene Antibiotics Based on a Ring‐Closing Metathesis and an Aldol Addition of a Lactone Enolate

“…We held the following factors responsible: 1) The separation of 45a from p ‐methoxybenzaldehyde, which resulted from the reaction of 44a and CAN, was difficult and caused losses of yield, 2) the corresponding silyl ether and acetal moieties made compounds 45a , 46a , and 47a acid‐sensitive in the flash chromatography column,69 and 3) compounds 45a and 47a were very volatile. We tried to exclude the last‐mentioned problem by increasing the molecular weight of silyl ether 44a by advancing to the alkenylstannane 48 (75 % yield)70 and converting the latter into the alkenyl iodide 49 (100 % yield) 71. However, both of these derivatives decomposed when we tried to cleave the PMB group with CAN (even though such cleavages are known in the presence of alkenyl iodides72).…”

Total Synthesis of Kanamienamide and Clarification of Biological Activity

“…Our synthesis was started from known alcohol 5 , which was synthesized from ( S )-Roche ester in four steps by a stereoselective crotylboration reaction developed by Roush (Scheme ). Alcohol 5 was converted into the corresponding tosylate, which was reduced with LAH to give olefin 7 . Oxidative cleavage of the olefin, followed by the Horner–Wadsworth–Emmons reaction with known phosphonate 4 afforded enone 9 .…”

“…To a stirred solution of known alcohol 5 (703 mg, 2.66 mmol) in THF (10 mL) at −78 °C was added n BuLi (2.6 M in hexane) (1.30 mL, 3.38 mmol) dropwise. The solution was stirred at −78 °C for 30 min; then, p -toluenesulfonyl chloride (667.3 mg, 3.50 mmol) was added, and the reaction mixture was allowed to warm to room temperature.…”

“…The N -Me-enamide adjacent to the enol ether of kanamienamide ( 1 ) was planned to be constructed by Buchwald amidation of vinyl iodide 2 . Vinyl iodide 2 could be synthesized by Mitsunobu lactonization of hydroxy carboxylic acid 3 , which could be derived from known phosphonate 4 , known alcohol 5 , and TFA· N -Me- l -Leu-OMe ( 6 ) using several reactions including the Horner–Wadsworth–Emmons reaction.…”

The synthesis and biological evaluation of a kabiramide C fragment modified with a WH2 consensus actin-binding motif as a potential disruptor of the actin cytoskeleton

“…The N-methyl formamide moiety was installed using a copper-catalysed amidation reaction, 9b,15 and those basic conditions caused partial isomerisation at C(6). 16,17 The diastereomers were not separated and the synthesis was pursued nonetheless, as we assumed that the ratio of diastereomers would not prevent a meaningful evaluation of our hypothesis about the biological activity of the final compounds. Thus, the cleavage of the trimethylsilyl group using AgNO 3 18 afforded the terminal alkyne 7a.…”