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DOI: 10.1055/s-0030-1259037
Synthesis of Lipophilic N 9-Benzylguanine Derivatives
Publication History
Publication Date:
10 November 2010 (online)
Abstract
Lipophilic N 9-benzylguanine derivatives were synthesized from the arylalkylation of 2-N-acetylguanine with substituted benzyl bromides.
Key words
2-N-acetylguanine - benzylation - nucleobases - regioselectivity - HMBC
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References and Notes
N ² -Acetyl- N 9 -(3,5-di- tert -butylbenzyl)guanine (9): Purification was achieved through flash chromatography using a CombiFlash® system (regioisomer 9 being more polar than regioisomer 10) with a gradient of CH2Cl2-MeOH (100:0→50:50) and subsequent recrystallization in EtOH-H2O (32%). ¹H NMR (400 MHz, DMSO-d 6): δ = 8.07 (s, 1 H, H-8), 7.31 (s, 1 H, ArH), 7.08 (s, 2 H, ArH), 5.27 (s, 2 H, CH2), 2.16 (s, 3 H, CH3), 1.23 (s, 18 H, 2 × t-Bu). ¹³C NMR (400 MHz, DMSO-d 6): δ = 173.5, 155.0, 150.8, 148.7, 147.9, 139.8, 135.9, 121.3, 121.1, 119.9, 46.7, 34.5, 31.1, 23.8. HRMS (ESI+): m/z [MH]+ calcd: 396.2400; found: 396.2408.
23N ² -Acetyl- N 7 -(3,5-di- tert -butylbenzyl)guanine (10): Purification was achieved through flash chromatography using a CombiFlash® system (regioisomer 9 being more polar than regioisomer 10) with a gradient of CH2Cl2-MeOH (100:0→50:50) and subsequent recrystallization in EtOH-H2O (32%). ¹H NMR (400 MHz, CDCl3): δ = 7.79 (s, 1 H, H-8), 7.39 (s, 1 H, ArH), 7.23 (s, 2 H, ArH), 5.53 (s, 2 H, CH2), 2.37 (s, 3 H, CH3), 1.29 (s, 18 H, 2 × t-Bu). ¹³C NMR (400 MHz, CDCl3): δ = 173.4, 156.8, 153.5, 151.8, 148.0, 142.8, 134.5, 122.7, 122.0, 112.2, 51.3, 34.9, 31.4, 24.1. HRMS (ESI+): m/z [MH]+ calcd: 396.2400; found: 396.2408.
24N 9 -(3,5-Di- tert -butylbenzyl)guanine (1): Purification was achieved through flash chromatography using a CombiFlash® system with a gradient of CH2Cl2-MeOH (100:0→50:50) and subsequent recrystallization in EtOH-H2O (71%). ¹H NMR (400 MHz, DMSO-d 6): δ = 10.67 (s, 1 H, NH), 7.76 (s, 1 H, H-8), 7.28 (s, 1 H, ArH), 7.11 (s, 2 H, ArH), 6.48 (s, 2 H, NH2), 5.13 (s, 2 H, CH2), 1.22 (s, 18 H, 2 × t-Bu). ¹³C NMR (400 MHz, DMSO-d 6): δ = 157.1, 153.8, 151.4, 150.8, 137.7, 136.5, 121.5, 121.2, 116.5, 46.5, 34.6, 31.3. HRMS (ESI+): m/z [MH]+ calcd: 354.2294; found: 354.2294.
25N ² -Acetyl- N 9 -[3,5-bis( tert -butyldimethylsilyloxy)-benzyl]guanine (11): Purification was achieved through flash chromatography using a CombiFlash® system (regioisomer 11 being more polar than regioisomer 12) with a gradient of CH2Cl2-MeOH (100:0→50:50) and subse-quent recrystallization in EtOH-H2O (33%). ¹H NMR (400 MHz, CDCl3): δ = 7.64 (s, 1 H, H-8), 6.27 (s, 3 H, ArH), 5.06 (s, 2 H, CH2), 2.36 (s, 3 H, CH3), 0.94 (s, 18 H, 2 × t-Bu), 0.16 (s, 12 H, 4 × CH3). ¹³C NMR (400 MHz, CDCl3): δ = 171.7, 157.2, 156.8, 149.3, 147.3, 139.3, 137.3, 120.5, 112.8, 112.0, 47.4, 25.7, 24.5, 18.3, -4.31. HRMS (ESI+): m/z [MH]+ calcd: 544.2775; found: 544.2778.
26
N
²
-Acetyl-
N
7
-[3,5-bis(
tert
-butyldimethylsilyloxy)-benzyl]-guanine
(12): Purification was achieved through flash chromatography
using a CombiFlash® system (regioisomer 11 being
more polar than regioisomer 12) with a
gradient of CH2Cl2-MeOH (100:0→50:50)
and subse-quent recrystallization in EtOH-H2O
(33%). ¹H NMR (400 MHz, CDCl3): δ = 7.75
(s, 1 H, H-8), 6.44 (s, 2 H, ArH), 6.30 (s, 1 H,
ArH), 5.41 (s, 2 H, CH2), 2.37 (s, 3 H,
CH3), 0.94 (s, 18 H, 2 × t-Bu), 0.16 (s, 12 H, 4 × CH3). ¹³C
NMR (400 MHz, CDCl3): δ = 173.5, 157.2,
156.5, 153.4, 148.4, 142.8, 137.1, 113.3, 112.3, 112.1, 50.8, 25.7,
24.6, 18.3,
-4.31. HRMS (ESI+): m/z [MH]+ calcd:
544.2775; found: 544.2777
N 9 -[3,5-Bis( tert -butyldimethylsilyloxy)benzyl]guanine (2): Purification was achieved through flash chroma-tography using a CombiFlash® system with a gradient of CH2Cl2-MeOH (100:0→50:50) and subsequent recrystal-lization in EtOH-H2O (66%). ¹H NMR (400 MHz, DMSO-d 6): δ = 10.58 (s, 1 H, NH), 7.73 (s, 1 H, H-8), 6.43 (s, 2 H, NH2), 6.29 (s, 2 H, ArH), 6.17 (s, 1 H, ArH), 5.08 (s, 2 H, CH2), 0.89 (s, 18 H, 2 × t-Bu), 0.12 (s, 12 H, 4 × CH3). ¹³C NMR (400 MHz, CDCl3): δ = 156.8, 156.2, 153.7, 151.2, 139.8, 137.4, 116.5, 111.7, 110.4, 45.3, 25.5, 17.9, -4.6. HRMS (ESI+): m/z [MH]+ calcd: 502.2670; found: 502.2667.