US4196280A
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Novel macrolactone derivatives and process of producing them
Assignee: Microbial Chemistry Research Foundation
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Filing: 1978-03-03
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Granted: 1980-04-01
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Expires: 1998-03-03
Abstract
Abstract By protecting the aldehyde group of a macrolide series antibiotics with a cyclic acetal or thioacetal, novel macrolide derivatives can be produced from the macrolide series antibiotics by releasing successively, the sugar moieties bonded to the macrolide antibiotics. The novel macrolide derivatives obtained by this invention, that is, the derivatives of a macrolide series antibiotics produced by releasing partially or wholly the sugar moieties bonded are useful as intermediates for producing novel macrolide series antibiotics.
Inventors
- 👤 Sumio Umezawa
- 👤 Hamao Umezawa
- 👤 Kuniaki Tatsuta
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 12:16
CPC Classifications
C; C07; C07H; C07H15/00; C07H15/02; C07H15/04; C07D; C07D313/00; C07D407/00; C07D407/02; C07D407/06; C07H17/00; C07H17/04; C07H17/08
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
238 words
A process of producing the aglycone of a macrolide compound of the formula (1) wherein A represents a carbonyl group or RO--< group; R represents a hydrogen atom, an acyl group, or a forosaminyl group; R 1 represents an aldehyde group protected by a cyclic acetal or a thioacetal; R 2 represents a hydrogen atom or an acyl group; R 3 represents a lower alkyl group; R 4 represents a hydrogen atom, a hydroxymethyl group, or mycinosyloxymethyl group; R 5 represents a methyl group or a methoxy group; R 6 represents a hydrogen atom or a methyl group; ˜ represents a single bond or a double bond; ---- represents a single bond, a double bond, or an oxiran-2,3-diyl group; and ------ means that the macrolactone ring forms a 16-membered ring or a 17-membered ring, which comprises reacting a macrolide compound of the formula (2) ##STR28## wherein B represents a hydrogen atom, a hydroxyl group, or an acylmycanosyloxy group ##STR29## R 7 represents an acyl group; and A; R 2 ; R 3 ; R 4 ; R 5 ; R 6 ; ˜ ; -----; and ------ have the same significance as in general formula (1) with a dihydric alcohol of up to 4 carbon atoms, a dithiol, of up to 4 carbon atoms or a mercapto-alcohol in the presence of an organic acid and then reacting the product with an oxidizing agent and an acylating agent, successively.
Claim 2
Dependent Claim
238 words
A process of producing the aglycone of a macrolide compound of the formula (1) wherein A represents a carbonyl group or RO--< group; R represents a hydrogen atom, an acyl group, or a forosaminyl group; R 1 represents an aldehyde group protected by a cyclic acetal or a thioacetal; R 2 represents a hydrogen atom or an acyl group; R 3 represents a lower alkyl group; R 4 represents a hydrogen atom, a hydroxymethyl group, or mycinosyloxymethyl group; R 5 represents a methyl group or a methoxy group; R 6 represents a hydrogen atom or a methyl group; ˜ represents a single bond or a double bond; ---- represents a single bond, a double bond, or an oxiran-2,3-diyl group; and ------ means that the macrolactone ring forms a 16-membered ring or a 17-membered ring, which comprises reacting a macrolide compound of the formula (2) ##STR28## wherein B represents a hydrogen atom, a hydroxyl group, or an acylmycanosyloxy group ##STR29## R 7 represents an acyl group; and A; R 2 ; R 3 ; R 4 ; R 5 ; R 6 ; ˜ ; -----; and ------ have the same significance as in general formula (1) with a dihydric alcohol of up to 4 carbon atoms, a dithiol, of up to 4 carbon atoms or a mercapto-alcohol in the presence of an organic acid and then reacting the product with an oxidizing agent and an acylating agent, successively.
Claim 3
Dependent Claim
214 words
A process of producing a macrolide compound represented by the formula ##STR30## wherein A represents a carbonyl group or RO--< group; R represents a hydrogen atom, an acyl group, or a forosaminyl group; R 1 represents an aldehyde group protected by a cyclic acetal or a thioacetal; R 2 represents a hydrogen atom or an acyl group; R 3 represents a lower alkyl group R 4 represents a hydrogen atom, a hydroxymethyl group, or mycinosyloxymethyl group; R 5 represents a methyl group or a methoxy group; R 6 represents a hydrogen atom or a methyl group; ˜ represents a single bond or a double bond; ---- represents a single bond, a double bond, or an oxiran-2,3-diyl group; and ------ means that the macrolactone ring forms a 16-membered ring or a 17-membered ring which comprises reacting the macrolide compound represented by the formula ##STR31## wherein R 7 represents an acyl group and A; R 2 , R 3 ; R 4 ; R 5 ; R 6 ; ˜; -----; and ------ have the same significance as in the above formula with a dihydric alcohol of up to 4 carbon atoms, a dithiol of up to 4 carbon atoms, or a mercaptoalcohol of up to 4 carbon atoms in the presence of an organic acid.
Claim 4
Dependent Claim
214 words
A process of producing a macrolide compound represented by the formula ##STR30## wherein A represents a carbonyl group or RO--< group; R represents a hydrogen atom, an acyl group, or a forosaminyl group; R 1 represents an aldehyde group protected by a cyclic acetal or a thioacetal; R 2 represents a hydrogen atom or an acyl group; R 3 represents a lower alkyl group R 4 represents a hydrogen atom, a hydroxymethyl group, or mycinosyloxymethyl group; R 5 represents a methyl group or a methoxy group; R 6 represents a hydrogen atom or a methyl group; ˜ represents a single bond or a double bond; ---- represents a single bond, a double bond, or an oxiran-2,3-diyl group; and ------ means that the macrolactone ring forms a 16-membered ring or a 17-membered ring which comprises reacting the macrolide compound represented by the formula ##STR31## wherein R 7 represents an acyl group and A; R 2 , R 3 ; R 4 ; R 5 ; R 6 ; ˜; -----; and ------ have the same significance as in the above formula with a dihydric alcohol of up to 4 carbon atoms, a dithiol of up to 4 carbon atoms, or a mercaptoalcohol of up to 4 carbon atoms in the presence of an organic acid.
Claim 5
Dependent Claim
26 words
A process according to claim 1 wherein the dihydric alcohol is a member selected from the group consisting of ethylene glycol, propylene glycol, 1,3-propanedoil and 2,3-butanediol.
Claim 6
Dependent Claim
13 words
A process according to claim 1 wherein the dihydric alcohol is ethylene glycol.
Claim 7
Dependent Claim
39 words
A process according to claim 1 wherein the reaction between the macrolide compound and a member selected from the group consisting of the dihydric alcohol, dithiol and mercapto alcohol is conducted in the presence of an anhydrous organic solvent.
Claim 8
Dependent Claim
12 words
A process according to claim 5 wherein the organic solvent is acetonitrile.
Claim 9
Dependent Claim
12 words
A process according to claim 5 wherein the organic solvent is chloroform.
Claim 10
Dependent Claim
16 words
A process according to claim 1 wherein the organic acid is p-toluenesulfonic acid or methanesulfonic acid.
Claim 11
Dependent Claim
13 words
A process according to claim 8 wherein the organic acid is p-toluenesulfonic acid.
Claim 12
Dependent Claim
17 words
A process according to claim 1 wherein the oxidizing agent is a perbenzoic acid or peracetic acid.
Claim 13
Dependent Claim
13 words
A process according to claim 10 wherein the oxidizing agent is m-chloroperbenzoic acid.
Claim 14
Dependent Claim
26 words
A process according to claim 1 wherein the acylating agent is a member selected from the group consisting of acetic anhydride, propionic anhydride and benzoic anhydride.
Claim 15
Dependent Claim
13 words
A process according to claim 12 wherein the acylating agent is acetic anhydride.
Claim 16
Dependent Claim
35 words
A process according to claim 1 wherein the reaction between the macrolide compound and a member selected from the group consisting of the dihydric alcohol, dithiol and mercapto alcohol is conducted at about room temperature.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1983-04-01 | 1983-10-01 | 1984-04-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-04-01 | 1987-10-01 | 1988-04-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-04-01 | 1991-10-01 | 1992-04-01 | $7700.00 | Window Closed / Lapsed |