Guaiane synthesis

SCHEME 20 The Vanderwal guaiane synthesis with RCM and rearrangement. 

A rather different approach to the hydroazulenic synthesis has been adopted by Hendrickson and Boeckman. Treatment of 1-cyclopentenylcarboxalde-hyde (411) with the pyrrolidine enamine of cyclopentanone (412) yielded the thermodynamically most stable adduct (413) which, on quaternization and base-induced fragmentation, gave the acid (414) in 25% yield. Furthermore, the acid (414) has been converted into the epoxide (415) and the (5-lactone (416), both of which are potential synthetic precursors of guaiane-type sesquiterpenoids, e.g. pseudoguaianolides. 

The total synthesis of the naturally occurring guaiane (+)-alismol was accomplished by G.L. Lange and co-workers using a free radicai fragmentation/eiimination sequence of an initial [2+2] de Mayo photocycloadduct. ... 

Transannular cyclizations of cyclodecadiene monoepoxides have been studied in exhaustive detail, particularly amongst natural germacranolides, because of their relevance to biogenetic models for the synthesis of eudesmane- and guaiane-type sesquiterpenes. " A full discussion of this topic is beyond the scope of this chapter, but the examples collected in equations (54-64) provide the reader with an in-... 

Nishitani, K., Nakamura, Y, Orii, R., Aral, C., and Yamakawa, K., Studies on the terpenoids and related alicyclic compounds. Part 43. Stereoselective intramolecular cyclization of P-alkoxycarbonyl-CO-formylallylsilanes into bicyclic a-methylene-y-lactones, Chem. Pharm. Bull., 41, 822, 1993. Kuroda, C., Ohnishi, Y, and Satoh, J.Y, Intramolecular cyclization of P-(aIkoxycarbonyl)allylsilane with conjugated ketone. A new entry to bicyclo[4.3.0]nonane. Tetrahedron Lett., 34, 2613, 1993. Kuroda, C., Inoue, S., Takemura, R., and Satoh, J.Y, Intramolecular cyclization of allylsilanes in the synthesis of guaian-8,12-olide. Stereoselective formation of trans- and cw-fused methylenelactones, 7. Chem. Soc., Perkin Trans. 1, 521, 1994. 

Scheme 2.38 depicts a relay dienyne metathesis transformation to afford the hydroazulene ring system [18m]. In the presence of the phosphine-free catalyst 6, substrate 103 used as an epimeric mixture underwent a completely regioselective domino cyclization due to exclusive attack of the ruthenium carbene at the terminal olefin followed by RCM with release of 2,5-dihydrofuran. Diastereomer 104 was then further elaborated to achieve a formal synthesis of the guaiane (—)-englerin A, which shows a highly selective action against renal cancer cell lines. 

Few months later, the same group reported an optimized reaction sequence for the synthesis of echinopines A and B based on a related cascade transformation to 110. Cascade prodnct 110 was further elaborated into the postulated biosynthetic guaiane-type intermediate 111, followed by a rutheninm-catalyzed cycloisomerization reaction to provide echinopines core (Scheme 7.63). 

Lange, G. L. and Gottardo, C., Synthesis of the guaiane ( )-ahsmol using a free radical fragmen-tation/elimination sequence. Tetrahedron Lett., 35, 8513-8516,1994. 

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