Dihydrocorynantheine synthesis

The synthesis of (-)-hirsutine (2-795) was concluded by removal of the Boc-group, condensation with methyl formate, and methylation of the formed enol moiety. In a similar manner as was described for 2-795, (+)-dihydrocorynantheine (2-797) [399] with the (3S)- and (15 k)-configuration was synthesized from ent-2-800. 

The first total synthesis of ( )-dihydrocorynantheine (54) (163) and ( )-corynantheine (52) (164) with normal stereo arrangement of the C-3, C-15, and C-20 hydrogens (a, 3, a, respectively) was published in full detail by van Tamelen and co-workers in 1969. [In preliminary form it has been published earlier (165, 166).]... 

Lactam 299 has later been synthesized by another route from ethyl trans-5-ethyl-2-oxo-4-piperidineacetate and 3-chloroacetylindole, which represents a new formal total synthesis of ( )-dihydrocorynantheine and related alkaloids (104). 

The stereoselective total synthesis of both ( )-corynantheidine (61) (170,171) (alio stereoisomer) and ( )-dihydrocorynantheine (172) (normal stereoisomer) has been elaborated by Szdntay and co-workers. The key intermediate leading to both alkaloids was the alio cyanoacetic ester derivative 315, which was obtained from the previously prepared ketone 312 (173) by the Knoevenagel condensation accompanied by complete epimerization at C-20 and by subsequent stereoselective sodium borohydride reduction. ( )-Corynantheidine was prepared by modification of the cyanoacetate side chain esterification furnished diester 316, which underwent selective lithium aluminum hydride reduction. The resulting sodium enolate of the a-formyl ester was finally methylated to racemic corynantheidine (171). 

The route used earlier338 in the partial synthesis of dihydro-epipleiocarpamine from dihydrocorynantheine has now been adapted to the synthesis of 16-epipleio-carpamine (134) from geissoschizine.80 The major modification required was the protection of the enolic hydroxy-group at C-17 in geissoschizine (92) by the formation of a carbonate ester with ethyl chloroformate following fission of the... 

The total structures of this alkaloid (XCVIIIa) and its dihydroderivatives (XCVIIIb) as well as a synthesis of the former have been reviewed (Vol. VII, p. 42). In the meantime, a total synthesis of dl-dihydrocorynantheine (Cllb) has been reported (69,70). 

Szantay s synthesis " of ( )-dihydrocorynantheine (Scheme 13) takes advantage of an unusual epimerization reaction" which occurs in quinolizidine-enamine... 

Finally, the conversion of dihydrocorynantheine and hirsutine (91) into 20a-ethyl-19,20-dihydro-16-epipleiocarpamine (106) and the base (107) constitutes a total synthesis of these compounds (Scheme 19). 

An account of Szantay s synthesis " of dihydrocorynantheine has been published, in Hungarian. ... 

Although a partial synthesis of rhynchophylline from dihydrocorynantheine was accomplished in 1961 the total synthesis of this oxindole alkaloid remained incomplete for a long time. In the synthesis finally reported by Banet o/., the spiro oxindole nucleus has been established at an early stage, followed by stepwise construction of the functionalized piperidine ring D. 

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