Process for conversion of oxotomaymycin to tomaymycin
First Claim
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1. A process for the preparation of a compound of the formula ##STR18## which comprises the steps of (1) converting oxotomaymycin of the formula ##STR19## to the corresponding 8-OH protected intermediate of the formula ##STR20## wherein R is a conventional phenolic hydroxyl protecting group;
- (2) reacting amide intermediate III with phosphorous pentasulfide or 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide in an inert organic solvent to produce the thioamide intermediate of the formula ##STR21## wherein R is as defined above;
(3) reacting intermediate IV with a (lower)alkyl halide or (lower)alkoxonium salt in an inert organic solvent and in the presence of base to produce the thioiminoether intermediate of the formula ##STR22## wherein R3 is (lower)alkyl and R is as defined above;
(4) optionally removing the C-8 hydroxyl protecting group of intermediate V to form an intermediate of the formula ##STR23## wherein R3 is as defined above;
(5) selectively reducing the thioiminoether moiety of intermediate V or intermediate VI in an inert solvent to produce a thiocarbinolamine intermediate of the formula ##STR24## wherein R and R3 are as defined above; and
(6) reacting intermediate VII or VIII with a mercuric salt in methanol to form the carbinolamine product of the formula ##STR25## wherein R is as defined above; and
, when the product obtained is compound IX, removing the hydroxyl protecting group R from intermediate IX so as to form the desired tomaymycin product I.
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Abstract
A new chemical procedure for conversion of the biologically inactive fermentation product, oxotomaymycin, to the antibiotic, tomaymycin is disclosed as well as novel intermediates employed in such procedure.
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Citations
18 Claims
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1. A process for the preparation of a compound of the formula ##STR18## which comprises the steps of (1) converting oxotomaymycin of the formula ##STR19## to the corresponding 8-OH protected intermediate of the formula ##STR20## wherein R is a conventional phenolic hydroxyl protecting group;
- (2) reacting amide intermediate III with phosphorous pentasulfide or 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide in an inert organic solvent to produce the thioamide intermediate of the formula ##STR21## wherein R is as defined above;
(3) reacting intermediate IV with a (lower)alkyl halide or (lower)alkoxonium salt in an inert organic solvent and in the presence of base to produce the thioiminoether intermediate of the formula ##STR22## wherein R3 is (lower)alkyl and R is as defined above;
(4) optionally removing the C-8 hydroxyl protecting group of intermediate V to form an intermediate of the formula ##STR23## wherein R3 is as defined above;
(5) selectively reducing the thioiminoether moiety of intermediate V or intermediate VI in an inert solvent to produce a thiocarbinolamine intermediate of the formula ##STR24## wherein R and R3 are as defined above; and
(6) reacting intermediate VII or VIII with a mercuric salt in methanol to form the carbinolamine product of the formula ##STR25## wherein R is as defined above; and
, when the product obtained is compound IX, removing the hydroxyl protecting group R from intermediate IX so as to form the desired tomaymycin product I. - View Dependent Claims (2, 3, 4)
- (2) reacting amide intermediate III with phosphorous pentasulfide or 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide in an inert organic solvent to produce the thioamide intermediate of the formula ##STR21## wherein R is as defined above;
- 5. An intermediate of the formula ##STR27## wherein R is a conventional phenolic hydroxyl protecting group.
- 7. An intermediate of the formula ##STR28## wherein R3 is (lower)alkyl and R is a conventional phenolic hydroxyl protecting group.
- 9. An intermediate of the formula ##STR29## wherein R3 is (lower)alkyl.
- 11. An intermediate of the formula ##STR30## wherein R3 is (lower)alkyl and R is a conventional phenolic hydroxyl protecting group.
- 13. An intermediate of the formula ##STR31## wherein R3 is (lower)alkyl.
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15. A process for the preparation of an intermediate of the formula ##STR32## wherein R is a conventional phenolic hydroxyl protecting group, which process comprises reacting an amide intermediate of the formula ##STR33## wherein R is as defined above with phosphorous pentasulfide or 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide in an inert organic solvent.
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16. A process for the preparation of an intermediate of the formula ##STR34## wherein R3 is (lower)alkyl and R is a conventional phenolic hydroxyl protecting group, which process comprises reacting an intermediate of the formula ##STR35## wherein R is as defined above with a (lower)alkyl halide or (lower) alkoxonium salt in an inert organic solvent and in the presence of base.
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17. A process for the preparation of an intermediate of the formula ##STR36## wherein R is (lower)alkyl, which process comprises removing the C-8 hydroxyl protecting group of an intermediate of the formula ##STR37## wherein R is a conventional phenolic hydroxyl protecting group.
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18. A process for the preparation of an intermediate of the formula ##STR38## wherein R is a conventional phenolic hydroxyl protecting group, which process comprises selectively reducing in an inert organic solvent and in the presence of base the thioiminoether moiety of an intermediate of the formula ##STR39## wherein R3 is (lower)alkyl and R is a conventional phenolic hydroxyl protecting group.
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