Addition of Purines to N-Boc Imines Generated in Situ in Water: Efficient Synthesis of Novel Acyclic Purine Azanucleosides

Hui Zhang; Chun-Xia Lian; Wei-Cheng Yuan; Xiao-Mei Zhang

doi:10.1055/s-0031-1291043

Synlett, Inhaltsverzeichnis

Synlett 2012; 23(9): 1339-1342
DOI: 10.1055/s-0031-1291043

letter

Addition of Purines to N-Boc Imines Generated in Situ in Water: Efficient Synthesis of Novel Acyclic Purine Azanucleosides

Hui Zhang

^aKey Laboratory for Asymmetric Synthesis & Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, P. R. of China, Fax: +86(28)85257883 eMail: xmzhang@cioc.ac.cn

^bGraduate School of Chinese Academy of Sciences, Beijing 100049, P. R. of China

,

Chun-Xia Lian

^aKey Laboratory for Asymmetric Synthesis & Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, P. R. of China, Fax: +86(28)85257883 eMail: xmzhang@cioc.ac.cn

,

Wei-Cheng Yuan

^aKey Laboratory for Asymmetric Synthesis & Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, P. R. of China, Fax: +86(28)85257883 eMail: xmzhang@cioc.ac.cn

,

Xiao-Mei Zhang*

^aKey Laboratory for Asymmetric Synthesis & Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, P. R. of China, Fax: +86(28)85257883 eMail: xmzhang@cioc.ac.cn

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Abstract

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Abstract

A mild, efficient and highly regioselective addition of purine derivatives to N-Boc imines generated in situ in water was developed for the first time. A wide range of novel acyclic purine azanucleosides were synthesized in moderate to high yields through this transformation. This methodology was also appropriate for some other N-heterocycles.

Key words

addition - nucleobases - sulfones - imines - nucleosides

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Referenzen

References

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10 General Procedure for Addition of Purines 1 with α-Amido Sulfones 2: N-Boc α-amido sulfone (0.2 mmol, 1.0 equiv), Na₂CO₃ (0.3 mmol, 1.5 equiv), and H₂O (2 mL) were put in a 10-mL glass vial equipped with a small magnetic stirring bar. To the solution was added purine derivative (0.24 mmol, 1.2 equiv). After stirring for the stipulated time at r.t., the mixture was diluted with H₂O (5 mL) and extracted with EtOAc (3 × 25 mL, for 3aa–3ak, 3ca and 3cj) or CHCl₃ (3 × 25 mL, for 3ba, 3da, 3ea, 3fa and 3ga). The organic layers were combined, dried over anhyd Na₂SO₄ and concentrated under reduced pressure. The residue was subjected to silica gel flash chromatography (EtOAc–hexanes, 1:5) to give the pure product
11 tert-Butyl Cyclohexyl (2,6-Dichloro-9H-purin-9-yl)methylcarbamate (3aa): yield: 97%; white solid; mp 182.7–183.3 °C. ¹H NMR (300 MHz, CDCl₃): δ = 8.15 (s, 1 H), 8.83 (br, 1 H), 5.63–5.69 (m, 1 H), 2.33 (br, 1 H), 1.65–2.02 (m, 4 H), 1.37 (s, 9 H), 0.83–1.36 (m, 6 H).¹³C NMR (75 MHz, CDCl₃): δ = 154.5, 152.6, 152.4, 151.8, 145.7, 131.3, 81.3, 69.4, 40.1, 29.4, 29.1, 28.1, 25.7, 25.2, 25.1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₇H₂₃Cl₂N₅NaO₂: 422.1121; found: 422.1138

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