Oxidation of 2-Hydroxynevirapine, a Phenolic Metabolite of the Anti-HIV Drug Nevirapine: Evidence for an Unusual Pyridine Ring Contraction
Abstract
:1. Introduction
2. Results and Discussion
2.1. Oxidation of the Metabolite 2-Hydroxy-NVP
2.2. Structural Characterization of the Oxidation Product 14
3. Experimental
3.1. Chemicals
3.2. General
Bonds (Å) | Angles (°) | ||||
---|---|---|---|---|---|
Molecule 1 | Molecule 2 | Molecule 1 | Molecule 2 | ||
O5’-C5’ | 1.2130(14) | 1.2138(14) | C2’-N1’-C5’ | 109.18(10) | 109.03(10) |
O2’-C2’ | 1.2146(14) | 1.2111(14) | N1’-C5’-C4’ | 108.74(10) | 109.01(9) |
O7-C7 | 1.2234(14) | 1.2219(14) | C3’-C4’-C5’ | 105.96(9) | 105.58(10) |
N1’-C5’ | 1.3981(15) | 1.3967(15) | C2’-C3’-C4’ | 109.12(10) | 109.50(9) |
N1’-C2’ | 1.3716(15) | 1.3715(14) | N1’-C2’-C3’ | 106.95(9) | 106.81(9) |
N12-C3’ | 1.3789(14) | 1.3814(14) | O5’-C5’-C4’ | 126.75(10) | 126.31(11) |
N12-C7 | 1.3750(14) | 1.3735(15) | O5’-C5’-N1’ | 124.50(10) | 124.67(11) |
N1-C2 | 1.3553(14) | 1.3497(14) | O2’-C2’-N1’ | 128.46(11) | 128.16(11) |
N1-C6 | 1.3378(14) | 1.3380(16) | O2’-C2’-C3’ | 124.60(10) | 125.00(10) |
N8-C2 | 1.3482(14) | 1.3498(14) | C4’-C3’-N12 | 138.20(10) | 137.70(11) |
N8-C9 | 1.4329(15) | 1.4299(15) | N12-C3’-C2’ | 112.67(10) | 112.79(9) |
C4’-C5’ | 1.4956(16) | 1.4967(16) | C5’- C4’-C6’ | 119.03(10) | 118.50(10) |
C3’-C4’ | 1.3517(15) | 1.3480(15) | C3’-C4’-C6’ | 135.01(11) | 135.88(11) |
C2’-C3’ | 1.5094(15) | 1.5087(16) | C7-N12-C3’ | 128.53(10) | 128.24(10) |
C3-C7 | 1.4806(16) | 1.4792(15) | O7-C7-N12 | 120.00(11) | 120.10(10) |
C2-C3 | 1.4408(15) | 1.4363(15) | N12-C7-C3 | 116.55(10) | 116.63(9) |
C5-C6 | 1.3836(16) | 1.3817(19) | O7- C7-C3 | 123.44(10) | 123.26(10) |
C4-C5 | 1.3826(17) | 1.3831(18) | C2-C3-C7 | 120.17(9) | 120.31(9) |
C3-C4 | 1.3925(15) | 1.3855(16) | C4-C3-C7 | 122.84(10) | 122.47(10) |
C9-C11 | 1.4933(16) | 1.4958(19) | C2-C3-C4 | 116.99(10) | 117.20(10) |
C9-C10 | 1.4975(18) | 1.4966(18) | N1-C2-C3 | 121.63(10) | 121.96(10) |
C10-C11 | 1.5029(18) | 1.4973(19) | C2-N1-C6 | 118.19(10) | 117.84(10) |
Torsion Angles (°) | N1-C6-C5 | 124.34(11) | 124.44(12) | ||
C4-C5-C6 | 117.81(10) | 117.79(12) | |||
N8-C9-C11-10 | −110.69(13) 70.12(12) | C3-C4-C5 | 120.92(10) | 120.71(12) | |
N8-C2-C3 | 121.32(10) | 121.47(10) | |||
Angles between planes (°) | N1-C2-N8 | 117.04(10) | 116.57(10) | ||
C2-N8-C9 | 123.66(10) | 123.40(10) | |||
Cyclopropyl-Main frame | 72.62(7) | 61.55(7) | N8-C9-C11 | 117.54(10) | 116.40(11) |
N8-C9-C10 | 120.07(11) | 119.08(11) | |||
C9-C11-C10 | 59.97(8) | 60.00(9) | |||
C9-C10-C11 | 59.70(8) | 59.95(9) | |||
C10-C9-C11 | 60.33(8) | 60.05(9) |
3.3. General Procedure for 2-Hydroxy-NVP (2) Oxidation
3.3.1. At pH 7.4
3.3.2. At pH 10
4. Conclusions
Acknowledgments
References and Notes
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Antunes, A.M.M.; Sidarus, M.; Novais, D.A.; Harjivan, S.G.; Santos, P.P.; Ferreira da Silva, J.L.; Beland, F.A.; Marques, M.M. Oxidation of 2-Hydroxynevirapine, a Phenolic Metabolite of the Anti-HIV Drug Nevirapine: Evidence for an Unusual Pyridine Ring Contraction. Molecules 2012, 17, 2616-2627. https://doi.org/10.3390/molecules17032616
Antunes AMM, Sidarus M, Novais DA, Harjivan SG, Santos PP, Ferreira da Silva JL, Beland FA, Marques MM. Oxidation of 2-Hydroxynevirapine, a Phenolic Metabolite of the Anti-HIV Drug Nevirapine: Evidence for an Unusual Pyridine Ring Contraction. Molecules. 2012; 17(3):2616-2627. https://doi.org/10.3390/molecules17032616
Chicago/Turabian StyleAntunes, Alexandra M. M., Muna Sidarus, David A. Novais, Shrika G. Harjivan, Pedro P. Santos, João L. Ferreira da Silva, Frederick A. Beland, and M. Matilde Marques. 2012. "Oxidation of 2-Hydroxynevirapine, a Phenolic Metabolite of the Anti-HIV Drug Nevirapine: Evidence for an Unusual Pyridine Ring Contraction" Molecules 17, no. 3: 2616-2627. https://doi.org/10.3390/molecules17032616