Bristol-myers Company

Biochem Pharma Inc.

Iaf Biochem International, Inc.

Shire Biochem, Inc.

Bernard R Belleau

Nghe Nguyen-Ba

Terrence W Doyle

Terry T Conway

Bing Yu Luh

Boulos Zacharie

Dilip M Dixit

Tarek S Mansour

Haolun Jin

Allan H Tse

Colleen A Evans

Gerry Kavadias

Denis Brillon

Gilles Sauve

Carlo Franchini

Paul Nguyen-Ba

Bing-Yu Luh

Processes for preparing substituted 1, 3-oxathiolanes with antiviral properties

2-Substituted-4-substituted-1,3-dioxolanes and use thereof

Disclosed are processes for preparing compounds of the formula (I) and pharmaceutically acceptable salts or esters thereof:

Processes for preparing substituted 1,3-oxathiolanes with antiviral properties

This invention relates to 1-amino thioacylbenzimidazoyl-2-one derivatives having the formula: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are defined herein. These compounds are useful as thioacylating reagents. This invention also relates to a process for producing cyclic and linear thiopeptides using the thioacylating reagents of this invention. This invention further relates to intermediate anilide compounds, which are produced by reacting an ortho phenylene diamine with an amino acid chain or peptide. This invention also relates to intermediate thioanilide compounds, which are produced by thionating the intermediate anilide compounds. This invention further relates to a process for producing the thioacylating reagents of this invention by cyclizing the intermediate thioanilide compounds.

1-amino thiorcyl benzimidazoyl-2-one compounds

There is provided novel 2-substituted-4-substituted-1,3-dioxolanes which are particularly useful as antiviral agents.

4-(purinyl bases)-substituted-1,3-dioxlanes

Methods and compositions for preventing or treating human immunodeficiency virus (HIV) infections characterized by 2-substituted-5-substituted-1,3-oxathiolanes.

2-substituted-5-substituted-1,3-oxathiolanes with antiviral properties

There are provided novel 2-substituted-4-substituted-1,3-dioxolanes which are particularly useful as antiviral agents.

4-(nucleoside base)-substituted-1,3-dioxolanes useful for treatment of

Novel p-alkoxyphenylthionophosphine sulfide dimers useful for preparing thiopeptides from peptides.

p-Alkoxyphenylthionophosphine sulfide dimers

There is described the stereoselective total synthesis by a variety of routes of novel suitably substituted .DELTA..sup.2,3 -1,4-morpholine-2-carboxylic acids possessing a fused .beta.-lactam ring in the 1,6-position and carrying a substituent cis to carbon 5 in the 7-position of the fused ring system represented by the general formula ##STR1## wherein Z is hydrogen or the residue of an ester group and X is acylamino. Also included in the invention are compounds of the above formula in which the carboxyl group at the 2-position is protected as by an easily cleavable ester group and salts of both the free acids and carboxyl-protected compounds. The compounds are potent antibacterial agents.

O-2-isocephem-4-carboxylic acid derivatives as antibacterial agents

There is described the stereoselective total synthesis by a variety of routes of novel suitably substituted .DELTA..sup.2,3 -1,4-morpholine-2-carboxylic acids possessing a fused .beta.-lactam ring in the 1,6-position and carrying a substituent cis to carbon 5 in the 7-position of the fused ring system represented by the general formula ##STR1## wherein Q is hydrogen, alkyl, aralkyl or --CH.sub.2 COOZ where Z is hydrogen or the residue of an ester group and X is amino, azido or acylamino. Also included in the invention are compounds of the above formula in which the carboxyl group at the 2-position is protected as by an easily cleavable ester group and salts of both the free acids and carboxyl-protected compounds. Those compounds in which X is acylamino and their physiologically hydrolyzed esters and pharmaceutically acceptable salts are potent antibacterial agents.

.DELTA..sup.2,3 -1,4-Morpholine-2-carboxylic acid derivatives as

The dextrorotatory and levorotatory isomers of 1,6-Carbamate-3N-carbethoxy-2,5-dideoxystreptamine (I) have been found to be very valuable intermediates useful in the preparation of totally synthetic aminoglycoside antibiotics. An example of such an aminoglycoside antibiotic is 5-deoxykanamycin A.

Total synthesis of 2,5-dideoxystreptamines

There is described the stereoselective total synthesis by a variety of routes of novel suitably substituted .DELTA..sup.2,3 -1, 4-morpholine-2-carboxylic acids possessing a fused .alpha.-lactam ring in the 1,6-position and carrying a substituent cis to carbon 5 in the 7-position of the fused ring system represented by the general formula ##STR1## wherein Q is hydrogen, alkyl, aralkyl or -CH.sub.2 COOZ where Z is hydrogen or the residue of an ester group and X is amino, azido or acylamino. Also included in the invention are compounds of the above formula in which the carboxyl group at the 2-position is protected as by an easily cleavable ester group and salts of both the free acids and carboxyl-protected compounds. Those compounds in which X is acylamino and their physiologically hydrolyzed esters and pharmaceutically acceptable salts are potent antibacterial agents.

O-2-Isocephem-4-carboxylic acid derivatives as antibacterial agents

There is described the stereoselective total synthesis by a variety of routes of novel suitably substituted .DELTA..sup.2,3 -1, 4-morpholine-2-carboxylic acids possessing a fused .beta.-lactam ring in the 1,6-position and carrying a substituent cis to carbon 5 in the 7-position of the fused ring system represented by the general formula ##STR1## wherein Q is hydrogen, alkyl, aralkyl or --CH.sub.2 COOZ where Z is hydrogen or the residue of an ester group and X is amino, azido or acylamino. Also included in the invention are compounds of the above formula in which the carboxyl group at the 2-position is protected as by an easily cleavable ester group and salts of both the free acids and carboxyl-protected compounds. Those compounds in which X is acylamino and their physiologically hydrolyzed esters and pharmaceutically acceptable salts are potent antibacterial agents.

There is described novel substituted .DELTA..sup.2,3 -1, 4-morpholine-2-carboxylic acids possessing a fused .beta.-lactam ring in the 1,6-position and carrying a substituent cis to carbon 5 in the 7-position of the fused ring system represented by the general formula ##STR1## wherein Q is hydrogen or alkyl and X is amino. Also included in the invention are compounds of the above formula in which the carboxyl group at the 2-position is protected as by an easily cleavable ester group and salts of both the free acids and carboxyl-protected compounds. The compounds and their physiologically hydrolyzed esters and pharmaceutically acceptable salts are useful as intermediates in the preparation of antibacterial agents.

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Westmount, Canada

Bernard R Belleau