Alkaloids from papaya

The papaya plant Carica papaya is a source of the known alkaloid (+)-carpaine (52, R=H) and also of the dehydro-carpaines-I (63) and -II (54) (C.-S. Tang, Phytochem., 

Hydrolysis of carpaine affords carpamic acid (65 n=7,R=H) the racemate of which has been synthesised (E. Brown and A. Bourgouin, Tetrahedron, 1975, 31, 1047) W-Benzyloxycarbonyl carpamic acid (65,n=7 R=C02CH2Ph), 2,2 -diphenyl disulphide 

Azimine (66) from the leaves of Azima tetracantha on hydrolysis provides (+)-azimic acid (55,R=H n=5), a total stereospecific synthesis of this compound, and also of (+)-carpamic acid, from (+)-glucose has been described (S. Hanessian and R. Frenette, Tetrahedron Letters, 1979, 3391). 

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Many dimeric piperidine alkaloids also occur in nature, e.g., carpaine which has been isolated from papaya leaves (Carica papaya) 175 the absolute configuration has been determined.176 Naturally occurring isoquinoline alkaloids177 exist in dimeric forms in some cases, e.g., the bisbenzylisoquinoline alkaloids which have two benzylisoquinoline nuclei joined together through one, two, or even three ether bridges an example is epistephanine isolated from Stephania japonica.178... 

Two new alkaloids of the carpaine group, dehydrocarpaine-I and -II, have been isolated from papaya leaves (Carica papaya L.). They have been formulated as (33) and (34) respectively, on spectral evidence and on the basis of their easy hydrogenation to carpaine. ... 

Application of the cyclization method to N-benzyloxycarbonylcarpamic acid (4) gives the bisbenzyloxycarbonyl derivative of the papaya alkaloid car-paine (5) in >50% yield. Carpaine itself is obtained from (5) by catalytic hydrogenation. In this case there is no evidence for formation of a monolactone in the cyclization. coocH,c,Hs... 

Evidence has been presented to the effect that pseudocarpaine, the minor alkaloid of Carica papaya, differs from carpaine (CXII) only in the stereochemistry of one of the methyl groups (iT S). 

C28H50N2O4, Mr 478.72, mp. 121 °C, [0] +21.65° (C2H5OH), monoclinic prisms. C., a macrocyclic symmetrical dilactide, is an alkaloid firom the leaves of the papaya tree (Carica papaya) which causes bradycardia (slowing of heart rate). It is an effective amoebi-cide and exhibits (in vitro) anti-tumor activity even at low concentrations. Derivatives of C. from C. papaya are the 2-epimer (pseudocarpaine), the 1,2-didehydro compound dehydrocarpaine /), and l,l, 2,2 -tetrade-hydrocarpaine (dehydrocarpaine II). 

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