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US 6,242,616 B1Granted
Synthetic techniques and intermediates for polyhydroxy, dienyl lactone derivatives
AssigneeThe Trustees of the University of Pennsylvania
InventorsAmos B. Smith, III, Thomas J. Beauchamp, Matthew J. LaMarche, Hirokazu Arimoto
Life of this patent
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Abstract
Synthetic methods for lactone-containing compounds such as the discodermolides are provided, as are compounds which mimic the chemical and/or biological activity thereof, and methods and intermediates useful in their preparation.
Claims14
A process for forming a tetraene of formula:
- wherein:
- R1, R2, R7, and R8 are independently C1-C10 alkyl;
- R3, R6, and R16 are independently selected from hydrogen and C1-C6 alkyl;
- R4 and R9 are independently an acid labile hydroxyl protecting group;
- R25 is an oxidatively labile protecting group;
- and
- J is selected from:
- wherein R32 is C1-C6 alkyl and R33 is an acid labile hydroxyl protecting group;
- the process comprising contacting a compound of the formula:
- J—CHO
- with a phosphonium salt of the formula:
- wherein R18 is C6-C14 aryl, in the presence of a base for a time and under conditions effective to form the tetraene.
9 more elements
A process for forming a tetraene of formula:
- wherein:
- R1, R2, R7, and R8 are independently C1-C10 alkyl;
- R3, R6, and R16 are independently selected from hydrogen and C1-C6 alkyl;
- and
- J is selected from:
- wherein R32 is C1-C6 alkyl and R33 is H;
- the process comprising contacting an alcohol of formula:
- wherein R4, R9, and R33 are acid labile hydroxyl protecting groups, with an isocyanate of the formula:
- X3CC(═O)NCO
- wherein X is a halogen, to form a trichloroaceryl carbamate intermediate;
- contacting the trichloroaceryl carbamate intermediate with neutral alumina to form a carbamate of formula:
- and;
- removing the acid labile hydroxyl protecting groups by contacting the carbamate with acid in a protic solvent to form the tetraene.
10 more elements
A compound of formula:
- wherein:
- R1, R2, R7, and R8 are independently C1-C10 alkyl;
- R3, R6, and R16 are independently selected from hydrogen and C1-C6 alkyl;
- R4, R9, and R14 are acid labile protecting groups;
- R40 is selected from OR25 and OC(═O)NH2;
- R25 is an oxidatively labile protecting group;
- and
- J is selected from:
- wherein R32 is C1-C6 alkyl and R33 is selected from H and an acid labile hydroxy protecting group.
6 more elements
A compound having the formula:
- wherein:
- R1, R2, R7, and R8 are independently C1-C10 alkyl;
- R3, R6, and R16 are independently selected from hydrogen and C1-C6 alkyl;
- R4, R9, and R14 are acid labile protecting groups;
- R40 is selected from OR25 and OC(═O)NH2;
- R25 is an oxidatively labile protecting group;
- and
- J is aryl.
5 more elements
Dependencies are inferred from the claim text.