A New Entry to 2-Substituted Purine Nucleosides Based on Lithiation-Mediated Stannyl Transfer of 6-Chloropurine Nucleosides

Abstract

In spite of exclusive lithiation at the 8-position of 9-(2,3,5-tris-O-TBDMS-β-d-ribofuranosyl)-6-chloropurine (2) with LDA, subsequent quenching of its lithiated species with Bu3SnCl (or TMSCl) results in the formation of 2-substituted products. Under optimized reaction conditions, where LTMP was used as a lithiating agent, 9-(2,3,5-tris-O-TBDMS-β-d-ribofuranosyl)-6-chloro-2-(tributylstannyl)purine (11) was formed in quantitative yield. Several experiments carried out to verify the reaction mechanism suggested that an anionic stannyl (or silyl) transfer from the 8- to the 2-position had been involved. Manipulation of the 2-tributylstannyl group in 11 and in its adenine counterpart (22) has disclosed a new entry to 2-substituted purine nucleosides. This chemistry was briefly applied to the synthesis of the 2-fluoro analogue of neplanocin A.

Molecular Design and Chemical Synthesis of a Highly Potent Epothilone

“…For the synthesis of these epothilones according to the retrosynthetic analysis of Figure 2, the corresponding heterocyclic stannanes were required. They were prepared either as shown in Scheme 1 (for compounds 26 a – b , 28 , 30 a – b , 32 , 33 , 35 a – c , and 37 a – b ) or by published procedures ( 35 b ,6 36 ,7 38 and 39 ,8 40 ,9 and 41 (commercially available)). The attachment of each heterocyclic moiety onto the epothilone scaffold was then carried out by Stille coupling4c of each stannane with vinyl iodide 22 10 to afford the targeted epothilones 5 – 21 as shown in Scheme 2.…”

Linear and convergent approaches to 2-substituted adenosine-5′-N-alkylcarboxamides

“…Preparation of 6-chloro-2-iodopurine (6) previously required a multiple step synthesis, such as the five-step process outlined by Taddei et al 9 In addition to the longer synthetic sequence needed, this approach also required relatively expensive reagents such as 2,2,6,6-tetramethylpiperidine, which were essential for the selective substitution of the 2-position. 10 The conversion of 6-chloro-2-iodopurine (6) to 2-iodoadenine (9) was subsequently investigated. Amination of 6-halogenated purines generally requires either a protecting group or a sugar at the N-9-position due to their poor solubility in most organic solvents.…”

Lithiation-Stannylation Chemistry for Nucleoside Synthesis

“…2 ' As a result of this study, it became possible to generate the hitherto unprecedented purin-2-yllithium by protecting 1 with 8-triisopropylsilyl group, the bulkiness of which prevents the above migration. This was exemplified by the preparation of 2-substituted adenosine derivatives, including the 2-fluoro derivative of nucleoside antibiotic neplanosin A, which has a cyclopentene ring instead of ribofuranose.…”