Pavinan alkaloids

The total synthesis of pavinane alkaloid platycerine (89) (Scheme 14) has been accomplished successfully (26) via 1-benzylisoquinoline derivative 91 obtained from Reissert intermediate 90. Quatemarization of 91 with methyl iodide followed by lithium aluminum hydride reduction supplied 1,2-dihydroisoquinoline 92, which on treatment with a 7 5 mixture of formic acid and phosphorous acid gave ( )-platycerine (89) in 60-70% yield. 

Tables I-III present the naturally occurring pavinane alkaloids reported so far, in alphabetical order with a key to their stmctures. A comprehensive listing of plant sources is given in Table IV.

Intermediates of the types 196 and 197 have been used in synthetic approaches to the pavinane and isopavinane alkaloids. ... 

Kagan s ether structurally related compounds have not been found in Nature but their nitrogen analogues belong to the pavine alkaloid family. Pavinan and isopavinan alkaloids can be formally viewed as oxidatively cyclised 1-benzyl-1,2,3,4-tetrahydroisoquinolines and are most frequently obtained by acid-catalysed cyclisation of appropriately oxidised congeners of these isoquinolines [13]. Numerous attempts have been made to convert Kagan s ethers into pavine, but all were unsuccessful [4]. 

The pavine alkaloids bisnorargemonine (54d) (566, 567), norargemonine (54e) (568), eschscholtzidine (54f) (569), platycerine (55b) (570), munitagine (55a) (571), and the newly isolated 2,9-dimethoxy-3-hydroxy-pavinane (54c) (221) were prepared synthetically. Studies of the reaction conditions of the synthesis led to an increase in the yields of pavinane... 

The isolation of the trioxygenated alkaloid (—)-2-hydroxy-3,8-dimethoxy-pavinane poses the interesting question of whether this compound is derived from (H-)-coclaurine or from (+)-reticuline. In either case, it is possible that a propavinane such as 17 could be involved in the biogenetic sequence. 

Rice KC (1982) Synthetic opium alkaloids and derivatives 2. Efficient total synthesis of (-)-dihy-drocodeinone and derivatives.. In Harris LS (ed) Problems of drug dependence 1981. NIDA Res Monogr 41, Washington DC, p 99 and references cited therein Rice KC, Brossi A (1980) Expedient synthesis of racemic and optically active N-norreticuline and N-substituted and 6 -bromo-N norreticulines. J Org Chem 45 592-601 Rice KC, Ripka WC, Reden J, Brossi A (1980) Pavinan and isopavinan alkaloids. Synthesis of racemic and natural thalidine, bisnorargemonine and congeners from N-norreticuline. J Org Chem 45 601-607... 

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