Takano s synthesis

New synthetic work in this area includes a description of the synthesis of dihydrocleavamine122 and an ingenious, brief synthesis of desethylibogamine.138 Takano s synthesis of ( )-20aH-dihydrocleavamine (231) involves an appropriate modification of the synthesis of ( )-quebrachamine, reported simultaneously. The essential starting material (232) was converted into (231) by the route outlined for the synthesis of quebrachamine in Scheme 20. 

This reaction has found its way into organic synthesis fi and is attractive because of its generality and selectivity. In Drummond s synthesis of hydroxymethylacylfulvene,3 0 for example, a Pauson-Khand reaction of the allene-alkyne 446 gave a 69% yield of 447. In this case, molybdenum hexacarbonyl was used. In Takano s synthesis of dendrobine, 448 was treated with dicobalt octacarbonyl and then NMO to give an 89%... 

Takano, S., Meriya, M., Ogasawara, K. (1991) EnantiocontroUed Total Synthesis of (—)-Physovenine and (—)-Physostigmine. Journal of Organic Chemistry, 56, 5982-5984. 

Takano s group reported the first enantioselective total synthesis of (—)-anti-rhine as well (146). Chiral product 235 was prepared via a number of stereoselective reactions. Reductive condensation of 235 with tryptamine, using sodium cyanoborohydride at pH 6, supplied lactam 236, which was reduced by di-isobutylalminum hydride to hemiacetal 237. The latter could be cyclized to (-)-antirhine by simple acid treatment (146). 

A summary of Takano s recent synthesis of ( )-quebrachamine (200), mentioned in last year s Report,22h is now accessible.122 The critical stages leading to a mixture of (206) and its epimer are outlined in Scheme 20 the remaining stages were carried out according to established methods. 

New synthetic work in this area includes syntheses of desethyldihydro-cleavamine (desethylquebrachamine),119" 20crH- and 20/IH-dihydrocleavamine,1196 and cleavamine.119" Takano s route to the dihydrocleavamines119ft is essentially an adaptation of his earlier synthesis of quebrachamine,119d while the synthesis of (-t-)-cleavamine (254) by Imanishi et al. consists in essence of a brief route to the unsaturated keto-lactam (255), which affords ( )-cleavamine and a hydroxy-cleavamine (256) (major product) on reduction (Scheme 35).119c... 

After the intense use of concerted reactions for natural product synthesis, the related metal-catalyzed cyclizations gained ground in the 1980s and 1990s. Several authors demonstrated the effectiveness of these reaction types for the synthesis of dendrobine (82). Takano et al. and Zard et al. used the Pauson-Khand reaction as a key step for their EPC-synthesis efforts (144,165,166). Mori et al. relied on the more stable zirkonacycle in a related key step (167-169), while Trost et al. employed a palladium-catalyzed alkylation as well as a palladium-catalyzed ene reaction as key steps (170). Takano s efforts ended with the tricyclic skeleton of dendrobine, whereas Mori and Trost finished their formal EPC-syntheses with intermediates of Kende s and Roush s racemic S3mtheses, respectively. Both completed dendrobine synthesis would have necessitated more than 20 steps. 

However, there has been no report on the highly stereoselective chiral synthesis of (- )-trachelanthamidine (100a) and ( + )-epilupinine (enr-lOOd) type alkaloids without the use of a chiral building block, except for Takano s chiral synthesis (33% optical purity) (81H(16)915),... 

Takano, S., Kasahara, C., Ogasawara, K. Enantioselective synthesis of the gibbane framework. J. Chem. Soc., Chem. Commun. 1981, 635-637. 

Hatakeyama, S., Satoh, K., Sakurai, K., and Takano, S., A synthesis of (-)-pyrenophorin using 4-DMAP-catalyzed ester exchange reaction of phosphonoacetates with lactols. Tetrahedron Lett., 28, 2717, 1987. 

---