Claims
- 1. A process for preparing di-N.sup.6', O.sup.3 -demethylistamycin A of the formula (I), which comprises the consecutive steps of:
- (a) protecting the four amino groups of 3',4'-dideoxyneamine of the formula (II) ##STR17## with an amino-protecting group of the formula ##STR18## where R.sup.1 is an alkyl group of 1-4 carbon atoms, a cycloalkyl group of 5-6 carbon atoms or a benzyl group, to produce a tetra-N-protected 3',4'-dideoxyneamine of the formula (II') ##STR19## wherein each R.sup.1 OCO-- stands for the monovalent amino-protecting group of urethane-forming type where R.sup.1 is as defined above,
- (b) converting this tetra-N-protected 3',4'-dideoxyneamine (II') into its 1,6-cyclic carbamate derivative by reacting with an alkali metal hydride, to produce said 1,6-cyclic carbamate derivative of the formula (II"): ##STR20## wherein R.sup.1 is as defined above, (c) protecting the 5-hydroxyl group of said 1,6-carbamate derivative (II") with a hydroxyl-protecting group (R.sup.2) which is selected from an alkyl group of 1-4 carbon atoms, benzyl group and tetrahydropyranyl group, to produce a compound of the formula (III) ##STR21## wherein R.sup.1 and R.sup.2 are as defined above, (d) treating the compound (III) with aqueous sodium or barium hydroxide to hydrolyze its 1,6-cyclic carbamate ring and thereby to produce the compound of the formula (III') ##STR22## wherein R.sup.1 and R.sup.2 are as defined above, (e) protecting the liberated 1-amino group of the compound (III') with an amino-protecting group --COR.sup.3 where R.sup.3 is an alkyl group of 1-4 carbon atoms, a cycloalkyl group of 5-6 carbon atoms or a benzyl group but must be different from the R.sup.1 present in the already existing amino-protecting groups ##STR23## to produce the compound of the compound of the formula (III") ##STR24## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above, (f) sulfonylating the 6-hydroxyl group of the compound (III") with a sulfonylation reagent of the formula R.sup.4 SO.sub.3 H where R.sup.4 is an alkyl group of 1-4 carbon atoms, an aryl group of 5-6 carbon atoms or a benzyl group, to produce a compound of the formula (IV) ##STR25## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined above, (g) reacting the compound (IV) with an alkali metal alcoholate to form a compound bearing an aziridine ring and having the formula (V): ##STR26## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above, (h) reacting the compound (V) with an alkali metal salt of a lower alkanoic acid or benzoic acid to open the aziridine ring of the compound (V) and thereby to produce a compound of the formula (VI): ##STR27## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above and R.sup.5 represents an acyl group which originates from the alkanoic or benzoic acid employed,
- (i) removing the two hydroxyl-protecting groups (R.sup.2 and R.sup.5) from the 3- and 5-positions of the compound (VI) to produce a compound of the formula (VII) ##STR28## wherein R.sup.1 and R.sup.3 are as defined above, (j) removing preferentially the amino-protecting groups (--COOR.sup.1) from the 1-, 2'- and 6'-positions of the compound (VII), and thereby to produce a compound of the formula (VII') ##STR29## wherein R.sup.3 is as defined above, (k) reducing the group (--NHCOOR.sup.3) of the compound (VII') with a metal hydride into the 4-methylamino group and thereby to produce the compound, N.sup.4 -deglycyl-di-N.sup.6', O.sup.3 -demethylistamycin A of the formula (VIII) ##STR30## (1) protecting the three 1-, 2'- and 6'-amino groups of the compound (VIII) with a known amino-protecting groups to produce a 1,2',6'-tri-N-protected derivative of the compound (VIII),
- (m) reacting said 1,2',6'-tri-N-protected derivative with glycine or an N-protected glycine derivative to acylate (glycylate) the 4- methylamino group of said 1,2',6'-tri-N-protected derivative and thereby to produce the 1,2',6'-tri-N-protected derivative of di-N.sup.6',O.sup.3 -demethylistamycin A, and
- (n) removing all the remaining amino-protecting groups from said 1,2',6'-tri-N-protected derivative of di-N.sup.6',O.sup.3 -demethylistamycin A to afford the desired di-N.sup.6',O.sup.3 -demethylistamycin A.
Priority Claims (1)
Number |
Date |
Country |
Kind |
55-38889 |
Mar 1980 |
JPX |
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Parent Case Info
This is a division of application Ser. No. 241,649 filed Mar. 9, 1981, now U.S. Pat. No. 4,379,687.
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4231924 |
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Nov 1980 |
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4251516 |
Martin et al. |
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4282211 |
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Aug 1981 |
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4382926 |
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4406891 |
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Divisions (1)
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Number |
Date |
Country |
Parent |
241649 |
Mar 1981 |
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