Total Synthesis of Isorosthin L and Isoadenolin I

Abstract

Total syntheses of two Isodon diterpenes, isorosthin L and isoadenolin I, are reported. The synthetic strategy features a quick assembly of two simple building blocks through a diastereoselective intermolecular aldol reaction and a subsequent radical cyclization for efficient construction of a rather complex advanced intermediate bearing a quaternary stereocenter present in all Isodon diterpenes. Oxidative cleavage of the CÀ C bond in the cyclopentane enabled the conversion to a lactone moiety which is desired for the construction of the molecular skeleton through reductive coupling with an aldehyde carbonyl group.

A unified strategy for the total syntheses of eribulin and a macrolactam analogue of halichondrin B

“…Attempts to induce macrocyclization of aldehyde methyl ester 42 employing SmI 2 ( 51 – 53 ) [or SmI 2 /LiCl or SmI 2 /hexamethylphosphoric triamide (HMPA)] unfortunately failed to produce the expected macrocycle 43 as depicted in Scheme 5 . Iodoaldehyde 44 was then converted to its tert -butyldimethylsilyl (TBS)-protected cyanohydrin derivative 45 , through the action of tert -butyldimethylsilyl cyanide (TBSCN) and KCN (87% yield), as a potential precursor of the expected macrocyclic TBS-protected hydroxynitrile derivative 46 , as shown in Scheme 5 .…”