Preparation of lysine based macromolecular highly branched homogeneous compound

• US 4,360,646 A
• Filed: 04/29/1981
• Issued: 11/23/1982
• Est. Priority Date: 04/06/1979
• Status: Expired due to Fees

• Current Assignee: Allied Corp. (Honeywell International Inc.)
• Original Assignee: Allied Corp. (Honeywell International Inc.)
• Inventors: Denkewalter, Robert G., Lukasavage, William J., Kolc, Jaroslav
• Primary Examiner(s): ANDERSON, HAROLD
• Application Number:
  US06/258,707
• Time in Patent Office: 573 Days
• Field of Search: 528/310, 528/328, 528/312, 525/420
• US Class Current: 525/420
• CPC Class Codes: C07K 14/001 by chemical synthesis
• CPC Class Codes: C08G 69/10 Alpha-amino-carboxylic acids polysuccinimides C08G73/1092
• CPC Class Codes: C08G 83/005 Hyperbranched macromolecules
• CPC Class Codes: C08H 1/00 Macromolecular products derived from proteins food proteins A23; glue, gelatine C09H

Abstract

Formed from trifunctional units (M) having attached, to one of the two terminal carbon atoms of an alkylene hydrocarbon diradical, the functional group A'"'"', and having attached, to the other terminal carbon atom, a different functional group B'"'"' reactive A'"'"' to form a linkage AB; and having attached, to a third carbon of the skeleton of unit (M), the functional group A" (preferably the same as A'"'"') reactive with B'"'"' whereby a macromolecule is built up of successive layers of units (M). The process involves successive stages in the first of which, the functional groups A'"'"' are blocked and group B is blocked with a "source" unit (S); then groups A'"'"' are liberated to form Compound I. In the second stage, Compound II is formed from the starting material (such as lysine) by first blocking groups A'"'"', then converting group B'"'"' to a form reactive with A'"'"'. Then a series of growth steps links two molecules of compound II to each molecule of Compound I via reaction between activated B'"'"' groups of two Compound II molecules, and two liberated A'"'"' groups of Compound I; and the four blocked groups A'"'"' in the two newly added units are liberated to form Compound III. In stage C, the four A'"'"' groups of Compound III are reacted as before with Compound II, and the eight blocked A'"'"' groups of the resultant newly added units (M) are liberated to complete the third stage; and so on, Lysine is illustrative of suitable starting materials. The products can be used as surface modifying agents; as metal chelating agents; and as substrates for preparation of pharmaceutical dosages.

Claims

1. Process of producing a macromolecule which comprises:

(A) an initiation stage wherein at least one source unit(S) is combined with at least one lysine unit by;

(1) blocking the two amino groups of lysine by conversion of each to a t-butyloxyurethane group;

thus protecting these amino groups against reaction with the carboxyl group;

(2) blocking the free carboxyl group of the obtained diurethane, N,N'"'"'-(di(t-butyloxycarbonyl) lysine, by conversion thereof to an inert N-substituted amide of said carboxyl group, inert toward amino groups;

(3) liberating the two lysine amino groups by hydrolysis of the two urethane groups whereby the t-butyloxycarbonyl groups are removed and decomposed to t-butanol and carbon dioxide;

thus freeing the two amino groups and obtaining a Compound I;

(B) a first growth stage wherein two lysine units (M) are linked to the lysine unit of Compound I by;

(1) blocking the two amino groups of the lysine unit in Compound I as in step (A) (1) above by conversion of each to a t-butyloxy urethane group;

(2) forming a Compound (II) by converting the free carboxyl group of the N,N'"'"'-di(t-butyloxycarbonyl) lysine, obtained in step (B) (1) above, to a carboxyl derivative reactive with amino groups;

(3) contacting the diamino-containing Compound (I), obtained in step (A)(3) above, with the reactive carboxyl derivative, Compound (II) of step (B)(2) above, to form the linkage --CONH-- and thereby link the lysine unit (M) of Compound I via its two amino groups to each of two diurethane lysine units (M) of Compound II via their carboxyl groups; and

then liberating the four blocked amino groups by hydrolysis of the four urethane groups as in step (A)(3) above thereby forming Compound III;

(C) as a third stage, repeating the steps, as in the preceding stage, of blocking the lysine amino groups;

coverting the carboxyls of such blocked lysines to a reactive derivative Compound II; and

linking four of these Compound II molecules via their reactive carboxyl derivative, to the four amino groups in each molecule of Compound III; and

then liberating the eight amino groups of the four newly added lysine units to form Compound IV;

(D) repeating at least once more, the set of growth steps of stage (C) above, thereby at each new stage increasing by a factor of essentially 2, the number of lysine units contained in the resulting macromolecule.

2. Process of claim 1 wherein Compound II, used at each stage to add lysine units by reaction between the lysine carboxyl derivative and lysine amino groups liberated at the prior stage, is the para-nitrophenyl ester of N,N'"'"'-di(t-butyloxycarbonyl) lysine.

3. Process of claim 1 wherein, as an additional stage, the macromolecule of lysine units is modified by reacting at least some of the free amino groups of a lysine unit with a reactive carboxyl derivative of at least one amino acid different from lysine, or with bromoacetic acid.