Lipase-mediated resolution of cis-1-amino-2-indanol, the key component of the HIV protease inhibitor indinavir

Anilkumar, A. T.; Goto, Kouhei; Takahashi, Tomiki; Ishizaki, Kōzō; Kaga, Harumi

doi:10.1016/s0957-4166(99)00260-8

Cited by 14 publications

(7 citation statements)

References 15 publications

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“…These searches have led to the discovery of new compounds, for example: sulphated polysaccharides from the giant kelp Durvillaea antarctica (Chamisso) Hariot (Matsuhiro et al 1996), and cytotoxic and viricidal trisulphated triterpene glycosides from the Antarctic sea cucumber (Staurocucumis liouvillei (Vaney)), which have been shown to be active against herpes simplex virus type I (HSV-I) at concentrations below 10 µg ml -1 (Maier et al 2001). In addition, the efficient and direct resolution of cis-1-amino-2-indanol using Candida antarctica lipase B catalysing the alcoholysis of its N, O-diacetyl derivative was also reported (Anilkumar et al 1999). A study of the immune response of the Anatarctic teleost Notothenia rossi to the bacteriophage MS2 was reported by O'Neill (1981), illustrating the potential significance of viruses to the Southern Ocean fisheries and bacterial ice nucleation activity after T4 bacteriophage infection was investigated by Kozloff et al (1992).…”

Section: Antarctic Viruses In Ecological Studiesmentioning

confidence: 99%

Viruses in Antarctic ecosystems

Pearce

Wilson

2003

Antartic science

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This review seeks to highlight the potential importance of viruses in Antarctic ecosystems and describe the limited scope of Antarctic virus studies to date, including studies of marine, terrestrial and freshwater communities. Although much of the existing work focuses on the microbial community, there are also studies of virus infection in Antarctic animal and plant populations. We describe methodologies available for the study of viral ecology in the field and in calling for a more intensive research effort discuss how microbial ecology might benefit from the study of viruses in Antarctic ecosystems.

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Section: Antarctic Viruses In Ecological Studiesmentioning

confidence: 99%

Viruses in Antarctic ecosystems

Pearce

Wilson

2003

Antartic science

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“…Candida antarctica lipase B was chosen based on its broad utility and general experience in our group 12. After exploring solvents,13 temperatures, and adding n -butanol,14 cephalosporin 4 was obtained (Table 1). Interestingly, when water was used as the nucleophile, low yields or no reaction was observed.…”

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confidence: 99%

Enzymatic Deprotection of the Cephalosporin 3′-Acetoxy Group Using Candida antarctica Lipase B

Patterson

Miller

2010

J. Org. Chem.

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Cephalosporins remain one of the most important classes of antibiotics. A useful site for derivatization involves generation of and chemistry at the 3′-hydroxymethyl position. While 3′-acetoxymethyl substituted cephalosporins are readily available, deacetylation to access the free 3′-hydroxymethyl group is problematic when the carboxylic acid is protected as an ester. Herein we report that this important transformation has been efficiently accomplished using Candida antarctica lipase B. Although this transformation is difficult to carry out using chemical methods, the enzymatic deacetylation has been successful on gram scale, when the cephalosporin is protected as either the benzhydryl or t-butyl esters, and on the corresponding sulfoxide and sulfone of the tbutyl ester.Cephalosporin antibiotics have been in use for more than 40 years and are still being employed to fight bacterial infections despite the rising incidence of resistance. 1 Decades of intense research have given rise to an arsenal of synthetic methods that have allowed many analogs to be prepared, including four generations of cephalosporins that have reached clinical use. 2 Although this research has led to many breakthroughs in cephalosporin-specific chemical methodology, accessing precursors for further elaboration is still not straightforward. Numerous derivatives have been made through modification at the 3′-hydroxymethyl group of cephalosporins. However, the deprotection of the common 3′-acetoxy precursor in the presence of the protected cephalosporanic acid, and without lactonization and/or double bond isomerization to give the Δ 2 isomer, has yet to be accomplished in a high yielding and reproducible manner (Scheme 1). Herein we report a selective enzymatic approach to the deprotection of the cephalosporin acetoxy group, using commercially available Candida antartica lipase B (CAL B), on acrylic resin. mmiller1@nd.edu. Supporting Information Available: Experimental methods for compounds 1-3 and 5-9, and all 1 H and 13 C NMR spectra. This material is available free of charge via the Internet at http://pubs.acs.org. Commercially available 7-amino cephalosporanic acid (7-ACA) was converted, in reasonable yields, to 3 using a modified literature procedure to introduce the t-butyl ester 4 and standard Schotten-Baumann conditions to install the phenylacetyl group as a simple representative side chain (Scheme 2). Despite considerable effort, the 3′-acetoxy substituent was unable to be removed in acceptable yields and in the absence of double bond isomerization using the following methods (see supporting information for details): saponification, 4 KCN, HCl, 5 TMSI/trifluoroacetate/pH 7.0, 6 or bis(tributyltin) oxide. 7 Based on these findings, enzymatic deacetylation methods were explored. NIH Public AccessEnzymatic deprotection of the cephalosporin acetoxy group has been demonstrated in the literature. 8 Similar to chemical deacetylations, 4,6,8c,d,f,9 the enzymatic deacetylation reactions have only been reported when the cephalosporin co...

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“…We also prepared N,O-diacetyl compound 9 in order to study its alcoholysis. 19 First we prepared the Cbz derivative (±)-8b, but no enzymatic resolution was carried out since this product gave, after 1 h, a complex and inseparable mixture. 6b No resolution was observed with compound (±)-8c.…”

Section: Resultsmentioning

confidence: 99%

Lipase-catalyzed resolution of anti-6-substituted 1,3-dioxepan-5-ols

Gruttadauria

Meo

Riela

et al. 2006

Tetrahedron: Asymmetry

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Abstract-Several anti-6-substituted 1,3-dioxepan-5-ols were kinetically resolved using an immobilized lipase (Amano PS-C II) in toluene in the presence of vinyl acetate at 30°C. This approach provided, in some cases, the alcohol and the acetate in high enantiomeric purity, depending on the nature of the substituent (R = N 3 , SePh, I, OBn) and the acetal group (unsubstituted or dimethyl). The role of the size of substituents is also discussed. Enantiopure anti-6-substituted 1,3-dioxepan-5-ols are useful building blocks.

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Lipase-mediated resolution of cis-1-amino-2-indanol, the key component of the HIV protease inhibitor indinavir

Cited by 14 publications

References 15 publications

Viruses in Antarctic ecosystems

Viruses in Antarctic ecosystems

Enzymatic Deprotection of the Cephalosporin 3′-Acetoxy Group Using Candida antarctica Lipase B

Lipase-catalyzed resolution of anti-6-substituted 1,3-dioxepan-5-ols

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