Cheimonophyllal

Six new bisabolane type sesquiterpenoids, cheimonophyllons A (1), B (2), C (3), D (4), E (5), and cheimonophyllal (6) were isolated from the culture fluid of the basidiomycete, Cheimonophyllum candidissimum. The compounds exhibited nematicidal, weak antifungal and antibacterial as well as cytotoxic activities. The main product, cheimonophyllon A (1) (C15H22O4), was also active in the Ames mutagenicity test.

The highly enantiocontrolled total syntheses of natural (+)-cheimonophyllon E (5) and (+)-cheimonophyllal (6), biologically intriguing oxygenated bisabolane-type sesquiterpenoids, have been completed. The present synthetic strategy featured the use of an asymmetric aldol-type reaction for preparing in the first synthetic step an optically active 6-C-substituted 3-methyl-2-cyclohexenone derivative. Thus, a Mukaiyama aldol reaction of 1-methyl-3-silyloxy-1,3-cyclohexadiene 31 with alpha,beta-unsaturated aldehyde 11 in the presence of a chiral (acyloxy)borane (CAB)-type Yamamoto catalyst 33 proceeded with high levels of both diastereo- and enantioselectivities. The predominant aldol adduct, syn-9, was transformed into gamma,delta-epoxy allylic alcohol 8 by a nine-step sequence, including the substrate-controlled 1,2-reduction of enone, syn-12, also the epoxidation of allylic alcohol 15. Epoxy-alcohol 8 underwent 5-exo-cyclization in a high regioselective manner under acidic conditions to produce a bicyclic key intermediate (+)-7, which was eventually efficiently converted to (+)-cheimonophyllon E (5) or (+)-cheimonophyllal (6).