EPOTHILONE SYNTHESIS BUILDING BLOCKS III AND IV: ASYMMETRICALLY SUBSTITUTED ACYLOINS AND ACYLOIN DERIVATIVES, METHODS FOR THEIR PRODUCTION AND METHODS FOR THE PRODUCTION OF EPOTHILONES B, D AND EPOTHILONE DERIVATIVES

1. An α-hydroxy ketone and/or α-hydroxy aldehyde compound of the general formula I:

wherein

R 1 is selected from the group consisting of H, methyl, CH n F 3-n (n=0-3), ethyl or propyl;

B 1 and/or B 2 stands for a single or double bond in the E-(trans) form, Z-(cis) form or E/Z-mixture; or an epoxide as E-(trans) form, Z-(cis) form or E/Z mixture and/or combinations thereof;

R 4 is H, methyl, ethyl, CH n F 3-n (n=0-3), or halogen;

R 5 is H or PG;

Nu is H or alkyl;

E is CH 3 , CH 2 OH, CH 2 OPG, CO 2 PG, CO 2 R or CH═O;

R is H, methyl or ethyl; and

PG designates a conventional protective group for the given coupling atom or the given functional group.

2. The compound according to claim 1 , wherein B 1 stands for a double bond in Z form or an epoxide.

3. The compound according to claim 1 or 2 , wherein R 1 is methyl.

4. The compound according to claim 1 , wherein B 2 stands for a single bond.

5. The compound according to claim 1 , wherein PG is selected from the froup consisting of: allyl, t-butyl, methyl, benzyl, silyl, acyl, an activated methylene derivative, methoxymethyl, alkoxyalkyl, 2-oxacycloalkyl, trimethylsilyl, triethylsilyl, dimethyl-tert-butylsilyl, acetyl, propionyl, benzoyl and tetrahydropyranyl.

6. The compound according to claim 1 , wherein the compound is not racemic, i.e. is optically active at the α-hydroxy position (at position 15) of the general formula I.

7. The compound according to claim 6 , wherein the absolute configuration of the α-hydroxy position of the general formula I (at position 15) corresponds to the natural configuration of epothilones at position C15.

8. The compound according to claim 1 , wherein the protective group PG is selected from the group consisting of: acetyl, propionyl, butyroyl and benzoyl groups.

9. The compound according to claim 1 , wherein the α-hydroxy group (at position 15) of the general formula I is protected by a non-racemic chiral acyl group.

10. The compound according to claim 9 , wherein the α-hydroxy group (at position 15) of the general formula I is esterified with optically active 2-methoxy mandelic acid.

11. A method for synthesising compounds according to claim 1 , comprising at least one of the following steps:

(a) reacting compounds of general formula II

wherein R 3 is selected from the group consisting of: alkyl, benzyl and phenyl or is a chiral, non-racemic residue R*; and

EWG is CO 2 PG;

with an allyl derivative of type A (coupled at X)

wherein X is selected from the group consisting of: Cl, Br, I, O-tosyl, methyl sulfonate, trifluor methyl sulfonate, alkanoates and aryl carboxylates;

to compounds with the general formula III

(b) performing a conversion of compounds of the general formula III to compounds of the general formula IV

by alkyl decarboxylation, sponification or decarboxylation;

(c) performing a solvolysis of the compound of general formula IV to free α-hydroxy ketones of the general formula I; and/or

(d) performing a racemate separation by esterification of compounds of the general formula I.

12. The method according to claim 11 , wherein R 3 is non-racemic chiral acyl group.

13. The method according to claim 11 , wherein the production of compounds of the general formula I or IV, which are non-racemic at the α-hydroxy position, is performed by separation of the racemates by enzymatic esterification.

14. The method according to claim 13 , wherein the esterification is performed in the presence of an enzyme selected from the group consisting of lipases and esterases.

15. The method according to claim 14 , wherein lipases from Pseudomonas cepacia and/or Candida antarctica or esterases from Pseudomonas fluorescens and/or Streptomyces diastatochromogenes are used.

16. The method according to claim 11 , wherein the production of compounds of the general formula I or IV, which are non-racemic at the α-hydroxy position, is performed by enzymatic hydrolytic racemate separation of compounds of type IV.

17. The method according to claim 16 , wherein hydrolysis is performed in the presence of an enzyme selected from the group consisting of: lipases and esterases.

18. The method according to claim 17 , wherein lipases from Pseudomonas cepacia and/or Candida antarctica or esterases from Pseudomonas fluorescens and/or Streptomyces diastatochromogenes are used.

19. A compound of the general formula XII

wherein

B 1 is a single or double bond;

E is selected from the group consisting of CH 2 OH, CH 2 OPG and CH═O;

X′ is selected from the group consisting of Cl, Br, I, O-tosyl, methyl sulfonate, trifluor methyl sulfonate, alkanoates and aryl carboxylates;

Z′ is O or OPG; and

PG is a protective group.