Farnesyl acetates, cyclization

Farnesyl acetate SCHEME 5 Successive polyolefinic cyclizations. 

Even if this explanation is correct, the specificity observed by Breslow in the cyclization of trans,trans-farnesyl acetate (392) remains remarkable (Scheme 145). Indeed, under the same conditions as above, 392 gives 395 in 20-30% yield. Considering the effect of the methyl substituent, as discussed above, and the trend to often observe a Cy6 rather than a Cy5 cyclization giving trans-decalin systems in bicycle formation (Section XI.2.A.a), the regioselectivity is not completely unexpected. More remarkable is the highly stereoselective reaction observed, since four asymmetric centers have been... 

In their second generation synthesis of ent-abudinol B (97) (Scheme 3.33) [68], farnesyl acetate 99 was selectively epoxidized at the two alkenes with ketone 42 and transformed into compound 101 via bromide 100. The cyclization of compound 101 with TMSOTfgave tricyclic compound 102, which was alkenated and preferentially epoxidized at the two trisubstituted alkenes with ketone 42 by careful control of the reaction conditions, leaving the 1,1-disubstituted alkene intact. The cyclization of diepoxide 103 with TMSOTfgave enf-abudinol (97) in 15% yield along with the alkene isomer and partially cyclized product. 

Upon irradiation, in acetonitrile/aqueous solution, of 1-cyanonapthalene in the presence of all trans-farnesyl acetate, the latter undergoes only cis,trans-isomerization via an electron-transfer process. " No products from any other reactions were isolated. However, when the same combination of molecules was irradiated in sodium dodecyl acetate micellar solution, the main product was the result of intramolecular cychzation (Scheme 33). The cyclization is stereo- and regioselective to yield a trans-fused product in which the water molecule has added stereoselectively. Such an amazing selective cychzation occurs only in a micellar medium. 

Further biosynthetic studies by Cane et have shown that the conversion of farnesyl pyrophosphate (15) into nerolidyl pyrophosphate (16) proceeds by a net syn (suprafacial) process and that the subsequent cyclization to cyclonerodiol (17) occurs in a trans manner (Scheme 4). This careful piece of work was achieved by incorporation studies with doubly labelled nerolidol and mevalonate precursors and then by ascertaining the chirality of the acetate derived by Kuhn-Roth oxidation through enzymatic conversion (malate synthase/fumarase incubation) into labelled malate. In a subsequent series of experiments with labelled precursors, Cane et have confirmed that (i) only the C-7 hydroxy-group in cyclonerodiol is derived from water whereas the C-3 hydroxy-group is derived... 

The biosynthesis of the illudins from C-acetates and variously stereo-specifically labelled mevalonates has been studied. The results are in accord with the cyclization of farnesyl diphosphate set out in 5.59 5.65. 

Analogous processes involving cyclizations and rearrangements of carbocations derived from farnesyl diphosphate produce a rich variety of structural types in the sesquiterpene series. We will have more to say about the chemistry of higher terpenes, especially the triterpenes, later in this chapter. For the moment, however, let s return to smaller molecules to complete the picture of how isoprenoid compounds arise from acetate. 

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