Modulators of the complement system

Claim 2

A compound selected from those of the formula: ##STR4## wherein M is a nontoxic pharmaceutically acceptable cation salt, wherein the salt forming moiety is selected from the group consisting of alkali metal, alkaline earth metal, aluminum, ammonia and substituted ammonia selected from the group consisting of trialkylamine (C 1 -C 6 ), piperidine, pyrazine, alkanolamine (C 2 -C 6 ) and cycloalkylamine (C 3 -C 6 ); B is selected from the group consisting of --NHCO--, --NHSO 2 --, --NHCH 2 -- and --NH--; and Z is a straight or branched chain alkylidene group --(CH 2 ) m --, where m is an integer 0-12, inclusive, with the proviso that when m is zero or one, B cannot be --NHSO 2 --.

Claim 3

The compound according to claim 1, tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]octanediamide.

Claim 4

The compound according to claim 1, tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]butanediamide.

Claim 5

The compound according to claim 1, tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 6

The compound according to claim 1, tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]hexanediamide.

Claim 7

The compound according to claim 1, tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]heptanediamide.

Claim 8

The compound according to claim 1, tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]decanediamide.

Claim 9

The compound according to claim 1, tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]propanediamide.

Claim 10

The compound according to claim 1, tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-β-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 11

A compound according to claim 1, tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]tetradecanediamide.

Claim 12

The compound according to claim 1, tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]ethanediamide.

Claim 13

The compound according to claim 1, tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]butanediamine.

Claim 14

The compound according to claim 1, tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]octanediamide.

Claim 15

The compound according to claim 1, tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]butanediamide.

Claim 16

The compound according to claim 1, tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 17

The compound according to claim 1, tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]hexanediamide.

Claim 18

The compound according to claim 1, tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]heptanediamide.

Claim 19

The compound according to claim 1, tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]decanediamide.

Claim 20

The compound according to claim 1, tetradecatriethylammonium N,N'-[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]propanediamide.

Claim 21

The compound according to claim 1, tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]tetradecanediamide.

Claim 22

The compound according to claim 1, tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]ethanediamide.

Claim 23

The compound according to claim 1, tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-β-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 24

The compound according to claim 1, tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]butanediamine.

Claim 25

A compound selected from those of the formula: ##STR5## wherein Y is selected from the group consisting of H and COCH 3 ; B is selected from the group consisting of --NHCO--, --NHSO 2 --, --NHCH 2 -- and --NH--; and Z is a straight or branched chain alkylidene group --(CH 2 ) m --, where m is an integer 0-12, inclusive, with the proviso that when m is zero or one, B cannot be --NHSO 2 --.

Claim 26

A compound selected from those of the formula: ##STR5## wherein Y is selected from the group consisting of H and COCH 3 ; B is selected from the group consisting of --NHCO--, --NHSO 2 --, --NHCH 2 -- and --NH--; and Z is a straight or branched chain alkylidene group --(CH 2 ) m --, where m is an integer 0-12, inclusive, with the proviso that when m is zero or one, B cannot be --NHSO 2 --.

Claim 27

The compound according to claim 24, N,N'-bis[4-[4-O-(α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]octanediamide.

Claim 28

The compound according to claim 24, N,N'-bis[4-[4-O-(α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]butanediamide.

Claim 29

The compound according to claim 24, N,N'-bis[4-[4-O-(α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 30

The compound according to claim 24, N,N'-bis[4-[4-O-(α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]hexanediamide.

Claim 31

The compound according to claim 24, N,N'-bis[4-[4-O-(α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]heptanediamide.

Claim 32

The compound according to claim 24, N,N'-bis[4-[4-O-(α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]decanediamide.

Claim 33

The compound according to claim 24, N,N'-bis[4-[4-O-(α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]propanediamide.

Claim 34

The compound according to claim 24, N,N'-bis[4-[4-O-(α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]tetradecanediamide.

Claim 35

The compound according to claim 24, N,N'-bis[4-[4-O-(α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]ethanediamide.

Claim 36

The compound according to claim 24, N,N'-bis[4-[4-O-(β-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 37

The compound according to claim 24, N,N'-bis[4-[4-O-(α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]butanediamine.

Claim 38

The compound according to claim 24, N,N'-bis[4-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]octanediamide.

Claim 39

The compound according to claim 24, N,N'-bis[4-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]butanediamide.

Claim 40

The compound according to claim 24, N,N'-bis[4-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 41

The compound according to claim 24, N,N'-bis[4-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]hexanediamide.

Claim 42

The compound according to claim 24, N,N'-bis[4-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]heptanediamide.

Claim 43

The compound according to claim 24, N,N'-bis[4-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]decanediamide.

Claim 44

The compound according to claim 24, N,N'-bis[4-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]propanediamide.

Claim 45

The compound according to claim 24, N,N'-bis[4-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]tetradecanediamide.

Claim 46

The compound according to claim 24, N,N'-bis[4-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]ethanediamide.

Claim 47

The compound according to claim 24, N,N'-bis[4-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 48

A method of modulating the complement system in a body fluid which comprises subjecting said body fluid to the action of an effective complement modulating amount of a pharmaceutically acceptable compound selected from those of the formula of claim 1.

Claim 49

The method according to claim 46, wherein the body fluid is blood serum.

Claim 50

A method of modulating the complement system in a warm-blooded animal which comprises administering to said warm-blooded animal an effective complement modulating amount of a pharmaceutically acceptable compound selected from those of the formula of claim 1.

Claim 51

The method according to claim 46 or 48, wherein the compound is tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]octanediamide.

Claim 52

The method according to claim 46 or 48, wherein the compound is tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]butanediamide.

Claim 53

The method according to claim 46 or 48, wherein the compound is tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 54

The method according to claim 46 or 48, wherein the compound is tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]hexanediamide.

Claim 55

The method according to claim 46 or 48, wherein the compound is tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]heptanediamide.

Claim 56

The method according to claim 46 or 48, wherein the compound is tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]decanediamide.

Claim 57

The method according to claim 46 or 48, wherein the compound is tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]propanediamide.

Claim 58

The method according to claim 46 or 48, wherein the compound is tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-β-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 59

The method according to claim 46 or 48, wherein the compound is tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]tetradecanediamide.

Claim 60

The method according to claim 46 or 48, wherein the compound is tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]ethanediamide.

Claim 61

The method according to claim 46 or 48, wherein the compound is tetradecasodium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]butanediamine.

Claim 62

The method according to claim 46 or 48, wherein the compound is tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]octanediamide.

Claim 63

The method according to claim 46 or 48, wherein the compound is tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]butanediamide.

Claim 64

The method according to claim 46 or 48, wherein the compound is tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 65

The method according to claim 46 or 48, wherein the compound is tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β -D-glucopyranosylthio]phenyl]hexanediamide.

Claim 66

The method according to claim 46 or 48, wherein the compound is tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]heptanediamide.

Claim 67

The method according to claim 46 or 48, wherein the compound is tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]decanediamide.

Claim 68

The method according to claim 46 or 48, wherein the compound is tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]propanediamide.

Claim 69

The method according to claim 46 or 48, wherein the compound is tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-β-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]pentanediamide.

Claim 70

The method according to claim 46 or 48, wherein the compound is tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]tetradecanediamide.

Claim 71

The method according to claim 46 or 48, wherein the compound is tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]ethanediamide.

Claim 72

The method according to claim 46 or 48, wherein the compound is tetradecatriethylammonium N,N'-bis[4-[2,3,6-tri-O-sulfo-4-O-(2,3,4,6-tetra-O-sulfo-α-D-glucopyranosyl)-β-D-glucopyranosylthio]phenyl]butanediamine.

Claim 73

The method according to claim 48, wherein the compound is administered internally.

Claim 74

The method according to claim 48, wherein the compound is administered topically.

Claim 75

The method according to claim 48, wherein the compound is administered periodontally in the oral cavity.

Claim 76

The method according to claim 48, wherein the compound is administered intra-articularly.

Claim 77

The method according to claim 48, wherein the compound is administered parenterally.

Claim 78

A process for the preparation of compounds of the formula: ##STR6## wherein M is a nontoxic pharmaceutically acceptable cation salt, wherein the salt forming moiety is selected from the group consisting of alkali metal, alkaline earth metal, aluminum, ammonia and substituted ammonia selected from the group consisting of trialkylamine (C 1 -C 6 ), piperidine, pyrazine, alkanolamine (C 2 -C 6 ) and cycloalkylamine (C 3 -C 6 ); B is selected from the group consisting of --NHCO--, --NHSO 2 --, --NHCH 2 --, and --NH--; and Z is a straight or branched chain alkylidene group --(CH 2 ) m --, where m is an integer 0-12, inclusive, with the proviso that when m is zero or one, B cannot be --NHSO 2 --; which comprises reacting 4-aminothiophenol in dimethoxyethane and sodium hydride in oil with a solution of acetobromo-α-D-maltose or cellobiose in dimethoxyethane, under an inert atmosphere, for 18 hours, subjecting the mother liquor to dry column chromatography on silica gel using the solvent system ethyl acetate:hexane (1:1) giving 4-aminophenyl 2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α(or β)-D-glucopyranosyl)-1-thio-α (or β)-D-glucopyranoside; then reacting with an appropriate acid chloride of the formula X--(CH 2 ) m --X, where X is COCl or SO 2 Cl and m is an integer 0-12 (with the proviso that when m is zero or one X cannot be SO 2 Cl), in dry pyridine:acetonitrile (1:1) under an inert atmosphere for 18-36 hours, extracting from a suitable organic solvent, giving a compound of the formula: ##STR7## where B and Z are as hereinabove defined, treating this acetylated derivative in ammonia saturated methanol at 0° C., or sodium in methanol, for 18-24 hours; extracting from absolute ethanol, giving the corresponding deacetylated derivative of the formula: ##STR8## where B and Z are as hereinabove defined, then converting to the tetradecatriethylammonium sulfate derivatives of the formula: ##STR9## where B and Z are as hereinabove defined and Y is NH + (C 2 H 5 ) 3 , by treating with triethylamine-sulfur trioxide complex in N,N-dimethylacetamide, under an inert atmosphere at 60°-65° C., for 66 hours; reacting with a cation-containing compound wherein the salt forming moiety is selected from the group consisting of alkali metal, alkaline earth metal, aluminum, ammonia and substituted ammonia selected from the group consisting of piperidine, pyrazine, alkanolamine (C 2 -C 6 ) and cycloalkylamine (C 3 -C 6 ), and thereafter precipitating in ethanol, giving the desired products.

Claim 79

A process for the preparation of compounds of the formula: ##STR6## wherein M is a nontoxic pharmaceutically acceptable cation salt, wherein the salt forming moiety is selected from the group consisting of alkali metal, alkaline earth metal, aluminum, ammonia and substituted ammonia selected from the group consisting of trialkylamine (C 1 -C 6 ), piperidine, pyrazine, alkanolamine (C 2 -C 6 ) and cycloalkylamine (C 3 -C 6 ); B is selected from the group consisting of --NHCO--, --NHSO 2 --, --NHCH 2 --, and --NH--; and Z is a straight or branched chain alkylidene group --(CH 2 ) m --, where m is an integer 0-12, inclusive, with the proviso that when m is zero or one, B cannot be --NHSO 2 --; which comprises reacting 4-aminothiophenol in dimethoxyethane and sodium hydride in oil with a solution of acetobromo-α-D-maltose or cellobiose in dimethoxyethane, under an inert atmosphere, for 18 hours, subjecting the mother liquor to dry column chromatography on silica gel using the solvent system ethyl acetate:hexane (1:1) giving 4-aminophenyl 2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α(or β)-D-glucopyranosyl)-1-thio-α (or β)-D-glucopyranoside; then reacting with an appropriate acid chloride of the formula X--(CH 2 ) m --X, where X is COCl or SO 2 Cl and m is an integer 0-12 (with the proviso that when m is zero or one X cannot be SO 2 Cl), in dry pyridine:acetonitrile (1:1) under an inert atmosphere for 18-36 hours, extracting from a suitable organic solvent, giving a compound of the formula: ##STR7## where B and Z are as hereinabove defined, treating this acetylated derivative in ammonia saturated methanol at 0° C., or sodium in methanol, for 18-24 hours; extracting from absolute ethanol, giving the corresponding deacetylated derivative of the formula: ##STR8## where B and Z are as hereinabove defined, then converting to the tetradecatriethylammonium sulfate derivatives of the formula: ##STR9## where B and Z are as hereinabove defined and Y is NH + (C 2 H 5 ) 3 , by treating with triethylamine-sulfur trioxide complex in N,N-dimethylacetamide, under an inert atmosphere at 60°-65° C., for 66 hours; reacting with a cation-containing compound wherein the salt forming moiety is selected from the group consisting of alkali metal, alkaline earth metal, aluminum, ammonia and substituted ammonia selected from the group consisting of piperidine, pyrazine, alkanolamine (C 2 -C 6 ) and cycloalkylamine (C 3 -C 6 ), and thereafter precipitating in ethanol, giving the desired products.