168960-18-7

Usage

Uses

Used in Pharmaceutical Industry:
Carbamic acid, [(1R,4S)-4-(hydroxymethyl)-2-cyclopenten-1-yl]-1,1-dimethylethyl ester is used as an intermediate in the synthesis of ent-Abacavir (Abacavir EP Impurity A) (A105015), which is an enantiomer of Abacavir (A105000). Abacavir is a carbocyclic 2''-deoxyguanosine nucleoside reverse transcriptase inhibitor and an anti-HIV drug used to treat HIV infection. Intracellular enzymes convert Abacavir to its active form, carbovir-triphosphate (CBV-TP), which selectively inhibits HIV reverse transcriptase by incorporating into viral DNA. Abacavir is metabolized in the liver by uridine diphosphate glucuronyltransferase and alcohol dehydrogenase, resulting in inactive glucuronide and carboxylate metabolites.

Upstream product

• 151792-53-9 tert-butyl (1R,4S)-(-)-3-oxo-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 168960-19-8 (1R,4S)-1-amino-4-(hydroxymethyl)-2-cyclopentene hydrochloride 
• 79200-56-9 (-)-2-azabicyclo[2.2.1]hept-5-en-3-one 
• 4157-02-2 cis 2-cyclopentene 1,4-dibenzoate 
• 168773-62-4 (1R,2S,4S)-1-<(tert-Butyloxycarbonyl)amino>-2-hydroxy-4-<(methoxymethoxy)methyl>cyclopentane 
• 168773-56-6 (1R,4S,6R)-6-Iodo-2-(p-methoxybenzyl)-2-azabicyclo<2.2.1>-3-heptanone 
• 168773-55-5 (1R,4S,6S)-6-Hydroxy-2-(p-methoxybenzyl)-2-azabicyclo<2.2.1>-3-heptanone 
• 168773-65-7 (1R,4S)-1-<(tert-Butyloxycarbonyl)amino>-4-(hydroxymethyl)-2-cyclopentene 
• 168773-57-7 (1R,4S)-2-(p-Methoxybenzyl)-2-azabicylo<2.2.1>heptane-3,6-dione 
• 168773-58-8 Trifluoro-methanesulfonic acid (1R,4S)-2-(4-methoxy-benzyl)-3-oxo-2-aza-bicyclo[2.2.1]hept-5-en-6-yl ester 
• 168773-38-4 (5S,6R)-5-<(tert-Butyldimethylsilyl)oxy>-6-<(benzyloxy)methyl>-2-piperidinone 
• 168773-26-0 (5S)-5-<(1R)-1-<(9-Phenyl-9-fluorenyl)amino>-2-(benzyloxy)ethyl>dihydrofuran-2(3H)-one 
• 49805-30-3 2-azabicyclo[2.2.1.]hept-5-en-3-one 

Downstream Products

• 136522-35-5 (1R,4S)-1-amino-4-hydroxymethyl-2-cyclopentene 
• 168960-19-8 (1R,4S)-1-amino-4-(hydroxymethyl)-2-cyclopentene hydrochloride 
• 141271-12-7 (1S, 4R)-(4-(2,5-diamino-6-chloro-4-pyrimidinyl)amino)-2-cyclopenten-1-methanol 
• 859147-56-1 N-1-[(1R,4S)-4-{(monomethoxytrityl)oxymethyl}cyclopent-2-en-1-yl]-5'-O-{bis(phenylthio)phosphoryl}-2',3'-O-isopropylideneadenosine 
• 859147-52-7 N-1-[(1R,4S)-4-{(monomethoxytrityl)oxymethyl}cyclopent-2-en-1-yl]-5',O-(tert-butyldimethylsilyl)-2',3'-O-isopropylideneadenosine 
• 859147-54-9 N-1-[(1R,4S)-4-{(monomethoxytrityl)oxymethyl}cyclopent-2-en-1-yl]-2',3'-O-isopropylideneadenosine 
• 859147-58-3 N-1-{(1R,4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl}-5,-O-{bis(phenylthio)phosphoryl}-2',3'-O-isopropylideneadenosine 
• 112966-73-1 [(1R,3S)-3-(6-amino-9H-purin-9-yl)cyclopentyl]methanol 
• 918492-98-5 (1α,4α)-4-(6-Chloro-9H-purin-9-yl)-2-cyclopentenyl-carbinol 

Relevant academic research and scientific papers

Optical pure amino alcohol hydrochloride preparation method

The invention relates to a preparation method for optically pure aminoalcohol hydrochloride. The optically pure aminoalcohol hydrochloride is any one selected from optically pure aminoalcohol hydrochloride 1 and optically pure aminoalcohol hydrochloride 2 and is prepared by subjecting a compound 4 to an esterification ring-opening reaction, an amino protection reaction, an ester reduction reaction and a deprotection salt forming reaction. The optically pure aminoalcohol hydrochloride 1 or optically pure aminoalcohol hydrochloride 2 prepared in the invention can be directly used for synthesis of abacavir and carbovir. The preparation method provided by the invention has the advantages of high product optical purity, stable product quality, high product yield, a small amount of environmental pollution, low production cost, easy industrialization, etc.

Application of phosphoramidate ProTide technology significantly improves antiviral potency of carbocyclic adenosine derivatives

We report the application of phosphoramidate pronucleotide (ProTide) technology to the antiviral agent carbocyclic L-d4A (L-Cd4A). The phenyl methyl alaninyl parent ProTide of L-Cd4A was prepared by Grignard-mediated phosphorochloridate reaction and resulted in a compound with significantly improved anti-HIV (2600-fold) and HBV activity. We describe modifications of the aryl, ester, and amino acid regions of the ProTide and how these changes affect antiviral activity and metabolic stability. Separate and distinct SARs were noted for HIV and HBV. Additionally, ProTides were prepared from the D-nucleoside D-Cd4A and the dideoxy analogues L-CddA and D-CddA. These compounds showed more modest potency improvements over the parent drug. In conclusion, the ProTide approach is highly successful when applied to L-Cd4A with potency improvements in vitro as high as 9000-fold against HIV. With a view to preclinical candidate selection we carried out metabolic stability studies using cynomolgus monkey liver and intestinal S9 fractions.

Synthesis of stable and cell-type selective analogues of cyclic ADP-ribose, a Ca2+-mobilizing second messenger. Structure-activity relationship of the N1-ribose moiety

We previously developed cyclic ADP-carbocyclic ribose (cADPcR, 2) as a stable mimic of cyclic ADP-ribose (cADPR, 1), a Ca2+-mobilizing second messenger. A series of the N1-ribose modified cADPcR analogues, designed as novel stable mimics of cAD

Therapeutic nucleosides

The present invention relates to intermediates useful for the preparation of certain compounds, for example, purine carbocyclic nucleosides.

An efficient, scalable synthesis of the HIV reverse transcriptase inhibitor Ziagen (1592U89)

Ziagen, (1S, cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2- cyclopentene-1-methanol, was synthesized from (1S,4R)-azabicyclo[2.2.1]hept- 5-en-3-one by efficient processes which bypass problematic steps in earlier routes. 2-Amino-4,6-dichloro-5-formamidopyrimidine is a key intermediate which makes possible an efficient construction of the purine from a chiral cyclopentenyl precursor.

Process for resolving mixtures of carbocyclic stereoisomers

PCT No. PCT/EP97/06782 Sec. 371 Date Aug. 6, 1999 Sec. 102(e) Date Aug. 6, 1999 PCT Filed Dec. 4, 1997 PCT Pub. No. WO98/24741 PCT Pub. Date Jun. 11, 1998A process for the preparation of carbocyclic stereoisomers of formulae (I), (I'), (IIA'), (IIB'), (VA') and (VB'), including enantiomerically pure (IIA'), (I) and (I') utilizing fractional crystallization of salts formed with a chiral base; a reducing agent; a protecting group removing agent or a protecting group providing agent.

Efficient functionalization of acylnitroso cycloadducts: Application to the syntheses of carbocyclic nucleoside precursors

1,4-cis-disubstituted cyclopentene precursors of carbocyclic nucleosides were readily prepared utilizing acylnitroso hetero Diels-Alder reactions and Pd(0)-catalyzed alkylation reactions as the key steps. The chemistry was explored in both racemic and asymmetric fashion. The hydroxymethyl components of the carbocyclic nucleoside precursors were obtained from nitromethyl groups under oxidative Nef conditions and may be further elaborated into a variety of compounds of potential biological interest.

Chirospecific Syntheses of Precursors of Cyclopentane and Cyclopentene Carbocyclic Nucleosides by -Coupling and Transannular Alkylation

A new method is reported for the preparation of enantiomerically pure (1R,2S,4S)-1-amino-2-hydroxy-4-(hydroxymethyl)cyclopentane, (1R,2R,4S)-1-amino-2-fluoro-4-(hydroxymethyl)cyclopentane, and (1R,4S)-1-amino-4-(hydroxymethyl)-2-cyclopentene, advanced precursors to carbocyclic nucleosides.The method involves initial conversion of D-serine into an aldehyde with 9-phenylfluorenyl protection at nitrogen and O-benzyl protection at oxygen.A -coupling of this aldehyde with a titanium homoenolate derived from tert-butyl 3-iodopropionate gave the corresponding anti-lactone in high yield.Regioselective hydrogenolysis of the amine protecting group, accompanied by intramolecular O- to N-cyclization formed a lactam.After suitable nitrogen protection and functional group manipulation, transannular alkylation afforded the corresponding 2-benzyl- or 2-(p-methoxybenzyl)-6-hydroxy-2-azabicyclo-3-heptanone.Functional group modification of the 2-benzyl analogue gave the resulting 6(S)-hydroxy and 6(R)-fluoro N-BOC imides; alternatively, the 2-(p-methoxybenzyl) analogue was converted to an N-BOC imide containing an olefinic linkage at C-5 and C-6 of the bicycle.Subjecting each of the N-BOC imides to a reduction-deprotection sequence than afforded the desired carbocyclic analogues.The -coupling method also allowed improved and expedient access to an advanced tribenzylated lactam previously used in the racemic syntheses of the hydroxylated alkaloids D-mannonolactam, deoxymannojirimycin, and prosopinone, providing a formal asymmetric synthesis of these alkaloids.

An Enantioselective Synthesis of cis-4-tert-Butoxycarbamoyl-1-methoxycarbonyl-2-cyclopentene - A Useful, General Building Block

The amino acid derivative in the title represents an important building block for the synthesis of a number of biologically important targets such as the antiviral carbanucleosides and amidinomycin.By using asymmetric palladium-catalyzed desymmetrization of meso-2-ene-1,4-diols, cis-1,4-dibenzoyloxy-2-cyclopentene can be converted to the enantiomerically pure title compound in only four steps.Chemoselective ester reduction allows entry into the domain of carbanucleosides, whereas double-bond reduction provides the precursor for amidinomycin.In an ancillary study, a facile diastereoselective cis-hydroxylation provides aminocyclopentitols, compounds that have proven to be potent glycosidase inhibitors. - Keywords: allylic substrates; amidinomycin; asymmetric syntheses; carbanucleosides; palladium catalysts