Sclareol microbial hydroxylation

Besides sclareol, the microbial hydroxylation of a number of other naturally found and easily available terpenes of the labdane family has been investigated, particularly in view of designing chemoenzymatic routes for the hemisynthesis of forskolin 25, an activator of adenylate cyclase used as a therapeutic agent, or for the generation of potentially active analogs. Actually, 1,9-dideoxyforskolin 26 invariably co-occurs with forskolin 25... 

Figure 3 Hemisynthesis of 3a-hydroxymanool 24 from 3p-hydroxy sclareol 17 or 3-oxosclareol 21, two microbial hydroxylation products, (a) CrOj, pyridine (b) AcCOCl, PhNMcz (c) pyrolysis id) KOH/water-MeOH (e) K-Selectride.

Aranda, G., M.S. Kortbi, J. Y. Lallemand et af, 1991. Microbial transformation of diterpenes Hydroxylation of sclareol, manool and derivatives by Mucorplumbeus. 47 8339-8350. 

A significant example of hydroxylation reactions of cyclic terpenic compounds is illustrated by the microbial metabolism of sclareol. Sclareol 14, a labdane diterpene, can be easily isolated from the essential oil of Salvia sclarea L. (Labiatae) (clary sage oil) or... 

Sclareolide 31, a minor constituent of some plant extracts, can be prepared by oxidation of sclareol or manoyl oxide derivatives. The microbial oxidation of sclareolide by M. plumbeus ATCC 4740 was less productive than the oxidation of sclareol, but afforded, beside 3 (3-hydroxy and 3-keto derivatives, a small amount of l 3-hydroxy sclareolide [18]. Similar results and, in addition, the formation of 1,3-dihydroxylated derivatives have been obtained by incubation with Curvularia lunata, in higher conversion yields [35]. Cephal-osporium aphidicola, a fiingus producing the hydroxylated diterpenoid aphidicolin, was shown to hydroxylate sclareohde at the 3 position and, in addition, to afford a 33,6p-dihydroxylated derivative in substantial yields [36]. 

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