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US 6,316,616 B1Granted
Parallel combinatorial approach to the discovery and optimization of catalysts and uses thereof
AssigneePresident and Fellows of Harvard College
InventorsEric N. Jacobsen, Matthew S. Sigman
Life of this patent
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Abstract
The present invention provides methods and compositions, i.e. synthetic libraries of candidate compounds, useful in the discovery and optimization of compounds which catalyze at least one chemical transformation. In certain instances, the subject compounds catalyze a chemoselective, regioselective, stereoselective or enantioselective transformation.
Claims13
A catalyst represented by the following structure:
- wherein
- B represents an optionally substituted aromatic or heteroaromatic group;
- C1, C2 and C3 each represent chiral carbon atoms;
- X represents O, S or NH;
- J represents a linker group with 2-6 heavy atoms in its backbone including at least one functional group capable of acting as a hydrogen bond donor;
- R103 represents either a hydrogen bond donor, a Lewis basic group, or a group with both characteristics;
- R104 represents an aliphatic or cycloaliphatic substituent of up to 20 carbons (preferably 2-10);
- R105 is absent, or represents one or more additional substituents of B selected from the group consisting of alkyl, alkenyl, alkynyl, acyl, thioacyl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, amidine, acetal, ketal, aryl, heteroaryl, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or —(CH2)m—R80;
- and
- R106 and R107 each independently represent alkyl, alkenyl, alkynyl, acyl, thioacyl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, amidine, acetal, ketal, aryl, heteroaryl, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or —(CH2)m—R80, or
- R106 and R107 taken together with C2 and C3 form a ring having from 4 to 8 atoms in the ring;
- R108 and R109each independently represent an alkyl, represent alkyl, alkenyl, alkynyl, acyl, thioacyl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, amidine, acetal, ketal, aryl, heteroaryl, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or —(CH2)m—R80, with the proviso that R108 and (C(X)R109) are not identical (this proviso is implied by the aforementioned chirality of C1);
- R80 represents an unsubstituted or substituted aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
- and
- m is an integer in the range 0 to 8 inclusive.
12 more elements
A catalyst represented by the following structure:
- wherein
- A represents an optionally substituted ring having from 4 to 8 atoms in the ring;
- B represents an optionally substituted aromatic or heteroaromatic group;
- C1 represents a chiral carbon atom;
- X represents O, S or NH;
- R103 represents either a hydrogen bond donor, a Lewis basic group, or a group with both characteristics;
- R104 represents an aliphatic or cycloaliphatic substituent of up to 20 carbons;
- R105 is absent, or represents one or more additional substituents of B selected from the group consisting of alkyl, alkenyl, alkynyl, acyl, thioacyl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, amidine, acetal, ketal, aryl, heteroaryl, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or —(CH2)m—R80;
- and
- R108 and R109 each independently represent an alkyl, represent alkyl, alkenyl, alkynyl, acyl, thioacyl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, amidine, acetal, ketal, aryl, heteroaryl, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or —(CH2)m—R80, with the proviso that R108 and (C(X)R109) are not identical (this proviso is implied by the aforementioned chirality of C1);
- R110 is absent, or represents one or more additional substituents of A selected from the group consisting of alkyl, alkenyl, alkynyl, acyl, thioacyl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, amidine, acetal, ketal, aryl, heteroaryl, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or —(CH2)m—R80,
- R80 represents an unsubstituted or substituted aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;
- and
- m is an integer in the range 0 to 8 inclusive.
11 more elements
A catalyst represented by the following formula:
- wherein
- X represents, independently for each occurrence, O, S, or NR;
- R, R1, R2, and R3 represent, independently for each occurrence, H, alkyl, aryl, heteroalkyl, or heteroaryl;
- R4 represents H, alkyl, heteroalkyl, aryl, heteroaryl, formyl, or acyl;
- R2 is absent or occurs no more than 4 times;
- and
- n is an integer selected from the range 0 to 2 inclusive.
4 more elements
Dependencies are inferred from the claim text.