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The synthesis of 6,6′‐cyclo‐6′‐deoxyhexofuranosyluracils via a diazomethane‐promoted ring‐enlargement reaction
Author(s) -
Sasson Isaac M.,
Otter Brian A.
Publication year - 1987
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570240543
Subject(s) - chemistry , diazomethane , methylene , ketone , epoxide , sodium borohydride , ether , ring (chemistry) , medicinal chemistry , enol , enol ether , organic chemistry , catalysis
The protected 5′‐oxo‐6,5′‐cyclouridine 13 reacts with diazomethane to afford mostly the spiro‐epoxide 18 (79%), but it also undergoes ring‐expansion to give the corresponding 5′‐oxo‐6,6′‐cyclonucleoside 16. Under the conditions of the reaction, ketone 16 reacts further with diazomethane to give the enol ether 20 (12% overall), the isomeric 4‐methoxy nucleoside 15 (2%), and the spiro‐epoxide 19 (4.4%). Acid hydrolysis of the enol ether 20 , followed by reduction of the resulting ketone with sodium borohydride, affords a separable mixture of the 5′S (L‐talo) and 5′R (D‐allo) methylene‐bridged cyclonucleosides 7 and 8 , respectively. From proton nmr measurements, it appears that the 6′‐methylene groups of these cyclonucleosides project towards the 2′,3′‐edge of the furanose ring.