Enzymatic Method for the Synthesis of Blockbuster Drug Intermediates – Synthesis of Five‐Membered Cyclic γ‐Amino Acid and γ‐Lactam Enantiomers

A very efficient enzymatic method was developed for the synthesis of cyclic γ-lactam and γ-amino acid enantiomers, intermediates for drugs with a prominent turnover (e.g., abacavir and carbovir), through the CAL-B-catalysed enantioselective (E > 200) hydrolysis of the corresponding N-Boc protected and unprotected racemic γ-lactams with H2O in iPr2O. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

[1]  F. Fülöp,et al.  Vapour-assisted enzymatic hydrolysis of β-lactams in a solvent-free system , 2008 .

[2]  W. Haefeli,et al.  Comparison of the induction of P-glycoprotein activity by nucleotide, nucleoside, and non-nucleoside reverse transcriptase inhibitors. , 2008, European journal of pharmacology.

[3]  B. Kearney,et al.  Pharmacokinetics of Coadministered Ritonavir-Boosted Elvitegravir and Zidovudine, Didanosine, Stavudine, or Abacavir , 2007, Journal of acquired immune deficiency syndromes.

[4]  U. Walker,et al.  Mitochondrial Toxicity of Tenofovir, Emtricitabine and Abacavir Alone and in Combination with Additional Nucleoside Reverse Transcriptase Inhibitors , 2007, Antiviral therapy.

[5]  R. Vaidyanathan,et al.  A chemoenzymatic synthesis of an androgen receptor antagonist , 2007 .

[6]  M. Wainberg,et al.  Strategies for the optimal sequencing of antiretroviral drugs toward overcoming and preventing drug resistance , 2007 .

[7]  F. Fülöp,et al.  The first direct enzymatic hydrolysis of alicyclic β-amino esters: A route to enantiopure cis and trans β-amino acids , 2007 .

[8]  B. Gazzard,et al.  Abacavir Plasma Pharmacokinetics in the Absence and Presence of Atazanavir/Ritonavir or Lopinavir/Ritonavir and Vice Versa in HIV-Infected Patients , 2007, Antiviral therapy.

[9]  B. Achari,et al.  A short and efficient synthesis of 5-hydroxymethylcyclopent-2-enol from d-glucose and its elaboration to the carbanucleoside (−)-carbovir , 2007 .

[10]  C. Cativiela,et al.  Stereoselective synthesis of ?-amino acids , 2007 .

[11]  F. Fülöp,et al.  An efficient enzymatic synthesis of benzocispentacin and its new six- and seven-membered homologues. , 2006, Chemistry.

[12]  M. J. Jordan,et al.  Enantiomers of cis-constrained and flexible 2-substituted GABA analogues exert opposite effects at recombinant GABA(C) receptors. , 2006, Bioorganic & medicinal chemistry.

[13]  A. J. Whitehead,et al.  Formal enantioselective synthesis of (-)-carbovir and (-)-abacavir: An application of the rhodium(I)-catalysed tandem hydrosilylation-intramolecular aldol reaction , 2005 .

[14]  V. Nair,et al.  The antiviral activity, mechanism of action, clinical significance and resistance of abacavir in the treatment of pediatric AIDS. , 2005, Current pharmaceutical design.

[15]  D. Cherbavaz,et al.  Metal coordination-based inhibitors of adenylyl cyclase: novel potent P-site antagonists. , 2003, Journal of medicinal chemistry.

[16]  F. Fülöp,et al.  Lipase-catalyzed enantioselective ring opening of unactivated alicyclic-fused beta-lactams in an organic solvent. , 2003, Organic letters.

[17]  F. Fülöp,et al.  Preparation of (1R,8S)- and (1S,8R)-9-azabicyclo[6.2.0]dec-4-en-10-one: Potential starting compounds for the synthesis of anatoxin-a , 2001 .

[18]  Y. Kawakami,et al.  Substitution vs. addition. Regioselective electro-bromination of benzofuran , 2001 .

[19]  Koichi Tanaka,et al.  Optical Resolution of 2-Azabicyclo[2.2.1]hept-5-en-3-one by Inclusion Complexation with Brucine , 2001 .

[20]  V. Gotor,et al.  Biocatalytic selective modifications of conventional nucleosides, carbocyclic nucleosides, and C-nucleosides. , 2000, Chemical reviews.

[21]  C. Perry,et al.  Abacavir , 2000, Drugs.

[22]  M. Martin,et al.  An Efficient, Scalable Synthesis of the HIV Reverse Transcriptase Inhibitor Ziagen® (1592U89) , 2000, Nucleosides, nucleotides & nucleic acids.

[23]  M. Crimmins.  New developments in the enantioselective synthesis of cyclopentyl carbocyclic nucleosides , 1998 .

[24]  A. W. Czarnik.  Web alert Combinatorial chemistry , 1997 .

[25]  H. Rapoport,et al.  Chirospecific Syntheses of Precursors of Cyclopentane and Cyclopentene Carbocyclic Nucleosides by [3 + 3]-Coupling and Transannular Alkylation , 1995 .

[26]  M. Milewska,et al.  Synthesis of optically active monothioimides with chirality due to sulphur substitution , 1994 .

[27]  R. Csuk,et al.  Biocatalytical transformations. IV. Enantioselective enzymatic hydrolyses of building blocks for the synthesis of carbocyclic nucleosides. , 1994 .

[28]  C. T. Evans,et al.  Development of the biocatalytic resolution of 2-azabicyclo[2.2.1]hept-5-en-3-one as an entry to single-enantiomer carbocyclic nucleosides , 1993 .

[29]  C. T. Evans,et al.  Synthesis of either enantiomer of cis-3-aminocyclopentanecarboxylic acid from both enantiomers of racemic 2-azabicyclo[2.2.1]hept-5-en-3-one , 1991 .

[30]  G. Arnett,et al.  Synthesis and antiviral activity of carbocyclic analogues of xylofuranosides of 2-amino-6-substituted-purines and 2-amino-6-substituted-8-azapurines. , 1984, Journal of medicinal chemistry.

[31]  H. W. Dickenson,et al.  Structure-activity studies on the activity of a series of cyclopentane GABA analogues on GABAA receptors and GABA uptake. , 1986, European journal of pharmacology.

[32]  R. Vince,et al.  Synthesis of Carbocyclic Aminonucleosides , 1978 .