Oxetanocin derivative

Asymmetric [2 + 2] cycloaddition reaction affords a practical means of synthesis of optically active cyclobutanes, which can be used as useful intermediates in organic synthesis [138]. Narasaka reported that asymmetric [2 -i- 2] cycloaddition between acryloyl oxazolidinone derivatives and bis(methylthio)ethylene proceeded with high enantios-electivity when catalyzed by TADDOL-derived titanium complex (Sch. 58) [139]. The cyclobutane product was transformed into carbocyclic oxetanocin analogs or (-n)-grand-isol [140]... 

Oxetanocins. Oxetanocin A (49), formerly oxetanocin, is the first naturally occurring oxetanose derivative and is isolated from bacillus megaterium (1,145). It inhibits gram-positive bacteria, herpes viruses, and human immunodeficiency virus (HIV) (146). The chemical synthesis of (49) and several derivatives has been reported (147). 

Similar to the ketene thioacetal. vinyl and alkynyl thioelhers react with 2-oxazolidinone derivatives of s ,/ -unsaturated acids to give the corresponding cyclobutanes and cyclobutenes with almost complete asymmetric induction0,31-35. From a [2 + 2] adduct, prepared by use of a chiral titanium Lewis acid, a carbocyclic analog of the four-membered nucleoside oxetanocin A has been readily prepared in optically pure form10. 

Fenoglio, L, Nano, G.M., Vander Velde, D.G., and Appendino, G., Chemistry and occurrence of taxane derivatives. XXV. Synthesis of azetidine-type taxanes. Tetrahedron Lett. 37 (18), 3203, 1996. Hoshino, H., Shimizu, N., Shimada, N., Takita, T., and Takeuchi, T., Inhibition of infectivity of human immunodeficiency virus by oxetanocin, J. Antibiot. 40 (7), 1077, 1987. 

The carbocyclic analogue of the trehalase inhibitor, trehazolin, has been prepared and reported to have potency indistinguishable from the natural product." The synthesis of other antibiotic-related cyclopentane derivatives such as analogues of mannostatin A, allosamidin (and allosamizolin) and a 4-membered carbocyclic thiazole analogue of oxetanocin, are covered in Chapter 19. 

Analogues of oxetanocin A to have been synthesized are the alkylphosphonic acid derivatives, 16, and carbocyclic analogues 17 and 18. Other analogues of oxetanocin are mentioned in Chapters 18 and 20. 

Electron-rich and electron-poor alkenes can react with each other in a [2 + 2] fashion to give cyclobutanes with Lewis acid catalysis. In the example below, the chiral catalyst (27) is a complex of titanium(IV) with a ligand derived from (-)-tartaric acid. In the presence of 10 mol% of this catalyst, a stepwise [2 + 2]-cycloaddition occurs to (26) affording the cyclobutane (28) with an e.e. of > 98%. The product was converted in a few steps to a carbocyclic analogue of the nucleoside antibiotics oxetanocins A and 0.00... 

The carbocyclic analogue of oxetanocin A 15 has been synthesized from cyclobutane precursors, and the further analogues 16 (both enantiomers) and 17 -19 have been prepared. Likewise the guanosine analogue of 15 and the phosphonate 20, 5-vinyluracil analogues of 15 and 16, and the adenine and 7-deazaguanosine derivatives of 3-hydroxymethyl cyclobutane have been synthesized. ... 

Condensation of the oxetan derivative (15) with silylated heterocycles did not lead to oxetanocin-like compounds, but instead L-threofuranosyl derivatives, mostly of a-configuration (16), could be isolated.33... 

Further syntheses of oxetanocin have been described. A branched-chain tetroside whose synthesis is covered in Chapter 14 was converted in standard steps to oxetanocin (17) together with its o(-anomer. Another sequence started from adenosine, and proceeded via a 3 -deoxy analogue to the diazoketone (18), which underwent the necessary ring contraction to give (19) on photolysis.An oxetanocin analogue derived from 3,5-anhydro-D-xylofuranose is mentioned in Chapters 20 and 22. 

Cyclopentane and Cydobutane Derivatives. - A review of applications and mechanistic aspects of the CpiZr induced direct ring contraction of hept-6-enose and hex-5-enose derivatives to cyclopentane and cyclobutane ring systems with emphasis on the application to oxetanocin synthesis has appeared. (See also Vol. 

The previously described 7-deazapurine carbocyclic nucleoside synthesis (see Scheme 1) indicated that the most efficient route to 22 would be via reaction of the protected chiral amine 23 with the dimethylacetal of 2-(2-amino-4,6-dichloropyrimidin-S yl)acetaldehyde followed by ring closure, hydrolysis and dqirotection. A review of the literature revealed two enantioselective routes to cyclobutyl derivatives that had been used in the chiral synthesis of carbocyclic oxetanocins and could be employed for preparing a precursor to 23. In one case, however, the initial step involved a [2-i-2]-cycloaddition reaction of not easily obtainable reagents in the presence of a chiral titanium compound as... 

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