Carbocyclic nucleoside antibiotic activity

Neplanocins. Neplanocins A—D and F (37—41) are carbocyclic nucleoside antibiotic products of Ampullariella regularis (1,4) that are structurally related to (36) in that they contain either a cyclopentene or epoxy cyclopentane ring (121,122). The chemical syntheses of (37—41) and the 3-deazaneplanocins have been reported (123—126). Compound (37), which is converted to its 5 -triphosphate, has potent antitumor and antiviral activities (127—129). It strongly inhibits SAM in cells and viruses (128—131) and is converted to the 3 -keto derivative by Tadenosylhomocysteine hydrolase (132,133). 

In the area of carbocyclic nucleoside antibiotics, hydrolysis of the racemic esters 40 (R= n-Bu or ii-CeHis) by the lipase from Candida rugosa proceeds with very high enantiomeric selectivity, and from the resolved materials both enantiomers of aristeromydn were made by an established route. The authors report that a previous similar method (Vol.21, p. 182) is not as enantioselective. In a new synthesis of neplanocin A (43), the alcohol 41, derived from D-ribose, was converted to the cyclopentene 42 using an intramolecular insertion reaction of an alkylidene carbene. The new stereocentre in 42 was mostly of the wrong P-configuration, but could be corrected by a process of desilylation, oxidation and borohydride reduction. The biosynthesis of neplanocin A (43) and aristero-mycin has been reinvestigated, and the cyclopentenone 44 has been proposed as an intermediate, which is converted to aristeromycin via neplanocin A without any bifurcation. The 3-deaza-analogue 45 of 5 - or-aristeromydn has been prepared, and the antiviral activity of it and of the 7-deaza-compound (Vol.27, p. 235) are reported. ... 

Other carbocyclic nucleosides which show some antibiotic activity are mentioned in Chapter 20. 

The Suami and Ogawa group has been particularly active in the field of carbocyclic polyols. The main line of their interest was confined to the synthesis of aminocyclitols, constituents of aminoglycoside antibiotics and their analogs. Besides, inosamines and aminocyclopentanepolyols obtained in their laboratory were utilized as substrates in synthesis of nucleoside analogs. A... 

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