Stemodane diterpenoids

Hanson JR, PB Reese, JA Takahashi, MR Wilson (1994) Biotransformation of some stemodane diterpenoids by Cephalosporium aphidicola. Phytochem 36 1391-1393. 

The Peterson olefination is known for its better performance compared to the corresponding Wittig process for hindered substrates. This is demonstrated in the first asymmetric synthesis of (+)-maritimol, a member of the stemodane diterpenoids (eq 66). Thus, the key step, a Thorpe-Ziegler annulation, requires a 1,5-dinitrile motif. This is achieved by the generation of an a-silyl boronate, obtained by BuLi deprotonation of trimethylsilylace-tonitrile and subsequent transmetalation with triisopropyl borate, which is then condensed with the tricyclic aldehyde. ... 

The key steps in the synthesis of the stemodane-type diterpenoids are again the retroaldol-aldol procedure. This was best demonstrated by the rearrangement of the ketal (103) to the epimeric alcohol (104), upon treatment with acid, in 60%... 

The first asymmetric total synthesis of (+)-maritimol, a diterpenoid natural product that possesses a unique tetracyclic stemodane framework was accomplished by P. Deslongchamps. To introduce the C12 stereocenter, the Enders SAMP/RAMP hydrazone alkylation was used. This stereocenter played a crucial role in controlling the diastereoselectivity of the key transannular Diels-Alder reaction later in the synthesis. The required SAMP hydrazone was formed under standard conditions using catalytic p-toluenesulfonic acid. Subsequent protection of the free alcohol as a f-butyidiphenylsilyl ether, deprotonation of the hydrazone with LDA and alkylation provided the product in high yield and excellent diastereoselectivity. The hydrazone was converted to the corresponding nitrile by oxidation with magnesium monoperoxyphthalate. 

Taking advantage of such biosynthetic abilities, Hanson s group has systematically investigated the biotransformation by C. aphidicola of some (more or less) related cyclic diterpenoids such as kaurane [63-65] or stemodane [66] derivatives. Interestingly, with most kaurane derivatives, the current hydroxylation at C-3 observed with the natural substrate was inhibited, but various other positions can be hydroxylated, including the 113, 16a, and 17 positions (Fig. 5), the later probably after the reduction of the 16,17 double bond took place. 

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