Dimer, cularine

Structural elucidation work on the cancentrine alkaloids has been concisely reviewed. A biogenetic proposal for these unusual morphine-cularine dimers was also advanced. 

C(14) or C(10)-to-nitrogen bonding arrangement. The position of the acetoxy-group in (316 R = Ac) and thus the hydroxy-group in cancentrine was determined by examination of their n.m.r. spectra and by n.o.e. measurements. Cancentrine is a unique dimeric alkaloid constructed from morphine and cularine subunits and represents a formidable challenge for biogenetic-type synthesis. 

With the exception of the dimeric alkaloids, which also contain a cularine skeleton (The Alkaloids, Vol. XIV, p. 407 and this Vol., p. 510) no other new alkaloids of this type have been found. 

From Dicentra canadensis Walp. three alkaloids of the dimeric type were isolated cancentrine (cularine-morphine dimer), which was originally... 

Cularine-Morphine Dimers.—A full paper on cancentrine has appeared, which also incorporates a possible biogenetic pathway. The structures of the related dehydrocancentrine-A (57) and -B (58) have been elucidated by a combination of physical and chemical methods. ... 

Since the isolation of the first cularine alkaloid, more than 40 years ago, two reviews in Vols. 4 and 10 of this treatise (7, 2) and chapters in the books of Shamma 3a, 3b) and Kametani 4a, 4b) have dealt with four representative alkaloids of the cularine group. In the last decade, more than 25 other alkaloids have been isolated and characterized, including several with modified structures and different oxidation states. This group of alkaloids is regularly reviewed in the Specialist Reports of the Chemical Society (Alkaloid Series) (5). A complete listing of cularine alkaloids was published in 1984 6). It is now accepted that the dibenzoxepine skeleton is the characteristic structure of cularine alkaloids, although these may have evolved from several well-differentiated biogenic routes. The cularine-morphine dimer cancentrine and its derivatives have been excluded from this chapter as there have been no reports since the last review in Vol. 14 of this treatise (7). 

Cancentrine, isolated from Dicentra canadensis (Goldie) Walp. Fumaria-ceae), is a dimeric base composed of a cularine unit joined to a morphinane unit by an unusual spiro bridge (darkened section). Two naturally occurring dehydrocancentrines are also known, namely, the yellow dehydrocancentrine-A, which possesses a C-8,14 double bond, and dehydrocancentrine-B, which is unsaturated between C-31 and -32. Catalytic reduction of either of these dehydro bases using Adams catalyst yields cancentrine. ... 

Only the cularine moiety of the cularinemorphine dimers (cancentrine and dehydroderivatives) have substituents at C-7, C-4 and C-5 In 1932 cancentrine was isolated by Manske from Dicentra canadensis (Goldie)Walp, but nearly 40 years passed before its structure was deduced (Clark et al. 1970). 

---