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US 5,708,163 AGranted
Synthesis of the breast tumor-associated antigen defined by monoclonalantibody MBRL and uses thereof
AssigneeSloan-Kettering Institute of Cancer Research
InventorsSamuel J. Danishefsky, Mark T. Bilodeau, Shuang Hua Hu, Tae Kyo Park, John T. Randolph, In Jong Kim, Philip O. Livingston
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Abstract
The present invention provides a process for synthesizing a compound having the structure: ##STR1## wherein R is H, as well as related oligosaccharides useful as a vaccine for inducing antibodies to human breast cancer cells in an adjuvant therapy therefor.
Claims7
A process for synthesizing a compound having the structure:
- ##STR81## wherein R is H which comprises:
- (a) (i) reacting a compound having the structure:
- ##STR82## with an epoxidizing agent under suitable conditions to form an epoxide;
- (ii) cleaving the epoxide formed in step (a) (i) under suitable conditions with R.sub.4 NF wherein each R is independently the same or different and is a linear or branched chain alkyl, aralkyl or aryl group to form a fluoroalcohol;
- and
- (iii) alkylating the fluoroalcohol formed in step (b) (ii) under suitable conditions with a non-nucleophilic base and an organic halide having the formula C.sub.6 H.sub.5 CH.sub.2 X wherein X is Br, Cl, I or F to form a compound having the structure:
- ##STR83## (b) treating a compound having the structure:
- ##STR84## with an epoxidizing agent under suitable conditions to form an epoxide;
- and
- (c) coupling the epoxide formed in step (b) with a compound having the structure:
- ##STR85## under suitable conditions to form a compound having the structure:
- ##STR86## (d) (i) alkylating the compound formed in step (c) (ii) under suitable conditions with a non-nucleophilic base and an organic halide having the formula C.sub.6 H.sub.5 CH.sub.2 X wherein X is Br, Cl, I or F;
- and
- (ii) de-silylating the compound formed in step (d) (i) under suitable conditions with R.sub.4 NF wherein each R is independently the same or different and is a linear or branched chain alkyl, aralkyl or aryl group;
- (iii) treating the compound formed in step (d) (ii) under suitable conditions with a metal alkoxide to form a deprotected disaccharide;
- and
- (iv) alkylating the disaccharide formed in step (d) (iii) under suitable conditions to form a selectively deprotected disaccharide having the structure:
- ##STR87## (e) (i) coupling the selectively deprotected disaccharide formed in step (d) (iv) with the compound formed in step (a) (iii) under suitable conditions to form a protected trisaccharide;
- and
- (ii) de-protecting the protected trisaccharide formed in step (e) (i) under suitable conditions to form a trisaccharide having the structure:
- ##STR88## wherein R is H.
18 more elements
A process for synthesizing a trisaccharide ceramide having the structure:
- ##STR89## which comprises:
- (a) synthesizing a trisaccharide having the structure ##STR90## wherein R is PMB;
- (b) (i) reacting the trisaccharide formed in step (a) with an epoxidizing agent under suitable conditions to form a trisaccharide epoxide;
- and
- (ii) reacting the trisaccharide epoxide formed in step (b) (i) with a compound having the structure:
- ##STR91## under suitable conditions to form a protected trisaccharide ceramide having the structure:
- ##STR92## (c) (i) acylating the ceramide formed in step (b) (ii) under suitable conditions;
- and
- (ii) selectively de-protecting the compound formed in step (c) (i) under suitable conditions to form the trisaccharide ceramide.
6 more elements
A process for synthesizing a mercaptotrisaccharide having the structure:
- ##STR93## which comprises:
- (a) coupling a compound having the structure:
- ##STR94## with a compound having structure:
- ##STR95## under suitable conditions to form a disaccharide having the structure:
- ##STR96## (b) coupling the disaccharide formed in step (a) (ii) with a compound having the structure:
- ##STR97## under suitable conditions to form a trisaccharide having the structure:
- ##STR98## (c) iodosulfonamidating the trisaccharide formed in step (b) under suitable conditions to form a iodosulfonamide having the structure:
- ##STR99## and (d) reacting the iodosulfonamide formed in step (c) under suitable conditions with a thiolate to form the mercaptotrisaccharide.
5 more elements
A process of synthesizing a hexasaccharide ceramide having the structure:
- ##STR100## which comprises:
- (a) coupling a compound having the structure:
- ##STR101## with a compound having the structure:
- ##STR102## under suitable conditions to form a compound having the structure:
- ##STR103## (b) (i) reacting the compound formed in step (a) with an epoxidizing agent under suitable conditions to form a hexasaccharide epoxide;
- and
- (ii) reacting the hexasaccharide epoxide with a stannyl ether having the structure:
- ##STR104## under suitable conditions to form a hexasaccharide alcohol;
- (c) acylating the hexasaccharide alcohol formed in step (b) (ii) under suitable conditions to form a hexasaccharide acetate having the structure:
- ##STR105## (d) reductively acylating the hexasaccharide acetate formed in step (c) under suitable conditions in the presence of palmitic anhydride to form a hexasaccharide ceramide;
- (e) desilylating the hexasaccharide ceramide under suitable conditions to form a partially deprotected hexasaccharide ceramide;
- (f) (i) reducing the partially deprotected hexasaccharide ceramide under suitable conditions to form a deprotected hexasaccharide ceramide acetate;
- and
- (ii) acylating the deprotected hexasaccharide ceramide acetate under suitable conditions to form a hexasaccharide ceramide peracetate;
- and
- (g) saponifying the hexasaccharide ceramide peracetate under suitable conditions to form the hexasaccharide ceramide.
13 more elements
A process of synthesizing a hexasaccharide ceramide having the structure:
- ##STR106## which comprises:
- (a) coupling a compound having the structure:
- ##STR107## with a compound having the structure:
- ##STR108## under suitable conditions to form a hexasaccharide having the structure:
- ##STR109## (b) (i) reducing the hexasaccharide formed in step (a) under suitable conditions in the presence of palmitic anhydride to form a palmitoyl amide;
- (ii) desilylating the palmitoyl amide with R.sub.4 NF wherein each R is independently the same or different and is a linear or branched chain alkyl, aralkyl or aryl group under suitable conditions to form a partially deprotected hexasaccharide;
- (iii) de-protecting the hexasaccharide formed in step (b) (ii) under suitable conditions to form a deprotected hexasaccharide;
- (iv) acylating the hexasaccharide formed in step (b) (iii) under suitable conditions to form a hexasaccharide ceramide peracetate;
- and
- (iv) saponifying the hexasaccharide ceramide peracetate under suitable conditions to form the hexasaccharide ceramide.
7 more elements
A process of synthesizing an allyl hexasaccharide having the structure:
- ##STR110## which comprises:
- (a) coupling a compound having the structure:
- ##STR111## with a compound having the structure:
- ##STR112## wherein R is H under suitable conditions to form a hexasaccharide having the structure:
- ##STR113## (b) (i) desilylating the compound formed in step (a) with R.sub.4 NF wherein each R is independently the same or different and is a linear or branched chain alkyl, aralkyl or aryl group under suitable conditions to form a partially deprotected hexasaccharide;
- (ii) de-protecting the hexasaccharide formed in step (b) (i) under suitable conditions to form a deprotected hexasaccharide;
- and
- (iii) peracylating the compound formed in step (b) (ii) under suitable conditions to form a hexasaccharide peracetate having the structure:
- ##STR114## (c) (i) reacting the hexasaccharide peracetate formed in step (b) (iii) with an epoxidizing agent under suitable conditions to form an hexasaccharide epoxide peracetate;
- (ii) treating the hexasaccharide epoxide peracetate formed in step (c) (i) with allyl alcohol under suitable conditions to form an allyl hexasaccharide peracetate;
- and
- (iii) saponifying the allyl hexasaccharide peracetate under suitable conditions to form the allyl hexasaccharide.
9 more elements
A process of synthesizing a hexasaccharide having the structure:
- ##STR115## which comprises:
- (a) coupling a compound having the structure:
- ##STR116## with a compound having the structure:
- ##STR117## under suitable conditions to form a compound having the structure:
- ##STR118## (b) (i) acylating the compound formed in step (a) under suitable conditions;
- and
- (ii) reacting the compound formed in step (b) (i) with an epoxidizing agent under suitable conditions to form an epoxide having the structure:
- ##STR119## (c) (i) treating the epoxide with R.sub.4 NF wherein each R is independently the same or different and is a linear or branched chain alkyl, aralkyl or aryl group under suitable conditions;
- and
- (ii) alkylating the compound formed in step (c) (i) under suitable conditions to form a compound having the structure:
- ##STR120## wherein R is H or acyl;
- (d) coupling the compound formed in step (c) (ii) with a compound having the structure:
- ##STR121## under suitable conditions to form the hexasaccharide.
10 more elements
Dependencies are inferred from the claim text.