Hasubanan alkaloids synthesis

Trauner, D., Porth, S., Opatz, T., Bats, J.W., Giester, G., Mulzer, J. New ventures in the construction of complex heterocycles. Synthesis of morphine and hasubanan alkaloids, Synthesis 1998, 653-664. 

Another application of this strategy is the construction of cyclic systems bearing 1,4-dissonant relationships. For example, the synthesis of the hasubanan alkaloid ring system 35. reported in 1972 by Evans [24], involves the Diels-Alder cycloaddition of a dienyl sulphoxide 32 with an endocyclic enamine 33, followed by a [2,3]-sigmatropic rearrangement of the resulting cycloadduct 34 (Scheme 5.21). 

The first asymmetric total synthesis of the hasubanan alkaloid (+)-cepharamine was completed by A.G. Schultz et al. In order to construct the c/s-fused A/-methylpyrrolidine ring, the advanced tetracyclic lactone was first converted to the primary carboxamide by treatment with sodium amide in liquid ammonia. Next the Hofmann rearrangement was induced with sodium hypobromite in methanol initially affording the isocyanate, which upon reacting with the free secondary alcohol intramolecularly gave the corresponding cyclic carbamate in excellent yield. 

Scheme 11)146a and several successful approaches to the unsubstituted hasubanan carbocyclic system (Scheme 12)146a 146ft have appeared. These outstanding reports further emphasize the applicability of enamine annelation reactions in alkaloid synthesis. 

Scheme 18.43 Diels-Alder/Mislow-Evans approach in synthesis of hasubanan alkaloid framework and an electronically complementary approach to a rearrangement substrate.—...

Castle and co-workers used a ring-closing metathesis strategy in their synthesis of the carbocyclic core of ( )-hasubanonine, a member of the hasubanan alkaloid family." Hasubanan alkaloids are of interest due to their structural similarity to morphine alkaloids. Treatment of diene 220 with a catalytic amount of 4 in refluxing dichloromethane furnished the desired phenanthrene core 221 in quantitative yield. Six additional steps were required to obtain the desired natural product. 

Kobayashi and coworkers have further translated the concept of CIC in their synthetic approach toward the synthesis of hasubanan alkaloid (Figure 7.5) Hasub-anonine (240) [90]. Although the biological activity of 240 has not been evaluated yet, stmcturally it is similar to morphine-related alkaloids and therefore may... 

Details of construction of the hasubanan skeletal ring system and total synthesis of functionally least complicated of hasubanan alkaloids have been reported earlier by T. Ibuka, K. Tanaka and Y. Inubushi, Tetrahedron Lett., 1611 (1969) Y. Inubushi, M. Kitano and T. Ibuka, Chem. Pharm. Bull. Japan, 19,1820 (1971). 

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