Process of vitamin K

1. A process of preparation of vitamin K 2 derivatives, represented by formula (I)

wherein n is an integer from 3 to 13,

comprising the steps of:

(a) reacting an α-sulfonyl carbanion generated in situ from a phenylsulfone of menadiol derivative of formula (II)

wherein R represents an allyl protecting group,

in the presence of an organometallic base,

with a polyprenyl halide of formula (VII)

wherein

X is a halogen atom selected from the group consisting of bromine, chlorine and fluorine atoms,

Y is H or —SO 2 Ph,

m is an integer from 0 to 5,

as an alkylating agent;

to yield a phenylsulfonyl derivative of menadiol of formula (VIII)

wherein R, Y, and m have the meaning defined above,

(b) removing the phenylsulfonyl groups from the menadiol derivative of formula (VIII) by reductive elimination, to yield a menadiol derivative of formula (IX)

wherein R and m have the meaning defined above;

(c) subjecting the menadiol derivative of formula (IX) to an oxidative deeterification, to yield a crude menadione compound of formula (I),

wherein

n is the integer from 3 to 13, and

(d) optionally, purifying the crude menadione compound of formula (I) to yield pure vitamin K 2 .

2. The process according to claim 1 , wherein the α-sulfonyl carbanion is generated by means of an alkali metal hexamethyldisilazyde in a polar aprotic solvent.

3. The process according to any of the preceding claims, wherein phenylsulfonyl groups are removed with sodium amalgam in MeOH, buffered with Na 2 HPO 4 .

4. The process according to any of the preceding claims, wherein the oxidative deesterification is accomplished with the use of Pd(OAc) 2 /Ph 3 P and 1,3-dimethylbarbituric acid.

5. The process according to any of the preceding claims, wherein the alkylating agent in (a) is the polyprenyl halide of formula (VII)

wherein

X is a halogen atom selected from the group consisting of bromine, chlorine and fluorine atoms,

Y is —SO 2 Ph,

m is an integer from 0 to 5.

6. The process according to any of the preceding claims, wherein the alkylating agent in (a) is the polyprenyl halide of formula (VII)

wherein

X is a bromine atom,

Y is —SO 2 Ph, and

m is an integer from 0 to 5.

7. The process according to any of the preceding claims, wherein the polyprenyl halide used as the alkylaing agent is obtained in a stepwise process of:

(i) coupling a phenylsulfonyl-geranyl unit of formula (III),

with a compound of formula (IV)

and repeating said coupling process with the use of compound of formula (IV) until a compound of formula (V) of desired chain length m is obtained

wherein

Y is —SO 2 Ph,

m is an integer from 1 to 4;

(ii) hydrolysis of the compound of formula (V), to yield a polyisoprenol derivative of formula (VI)

wherein Y is —SO 2 Ph, and

m is an integer from 0 to 5;

(iii) optionally, removing the phenylsulfonyl groups to yield a polyisoprenol derivative of formula (VI)

wherein Y is H, and

m is defined above,

and

(iv) substituting the hydroxyl group of the compound of formula (VI) for a halogen atom selected from the group consisting of bromine, chlorine, an fluorine atoms in a reaction with a halogenating agent, to yield a polyprenyl halide of formula (VII),

wherein X is a halogen atom selected from the group consisting of bromine, chlorine and fluorine atoms,

Y is H or —SO 2 Ph, and

m is defined above.

8. The process according to any of the preceding claims, wherein MK-7 type of vitamin K2 is obtained.

9. New menadiol phenylsulfone compound of formula (II)

wherein R is an allyl protecting group.

10. A process of preparation of the menadiol phenylsulfone of formula (II)

wherein R of formula (II) represents the allyl protecting group,

in a Friedel-Crafts reaction catalysed by a Lewis acid, wherein InCl 3 is used as the Lewis acid in the presence of a solid inorganic base as an alkylation promoter.

11. The process according to claim 10 , wherein Na 2 CO 3 or K 2 CO 3 is used as the solid inorganic base.

12. An intermediate compounds selected from the group comprising of:

wherein

R is an allyl protecting group,

m is an integer from 0 to 5, and

n is an integer from 0 to 5.

13. The process according to claim 2 , wherein the alkali metal hexamethyldisilazide is sodium hexamethyldisilazyde.

14. The process according to claim 2 , wherein the polar aprotic solvent is selected from the group consisting of tetrahydrofuran, dimethylformamide, hexamethylphosphoramide, and mixtures thereof.

15. The intermediate compound of claim 12 , wherein said intermediate compound is:

wherein

m is an integer from 1 to 5.

16. The intermediate compound of claim 12 , wherein said intermediate compound is:

wherein

R is an allyl protecting group, and

n is an integer from 0 to 5.

17. The process according to claim 1 , wherein (d) occurs.

18. The process according to claim 7 , wherein (iii) occurs.