6-alkenyl-, 6-alkinyl- and 6-epoxy-epothilone derivatives, process for their production, and their use in pharmaceutical preparations

An epothilone compound of formula I,

• in which
• R1a, R1b are the same or different and mean hydrogen;
• C1-C10 alkyl, C6-C12 aryl, or C7-C20 aralkyl, each optionally substituted;
• or taken together a —(CH2)m— group with m=1, 2, 3, 4 or 5 or a —(CH2)—O—(CH2)— group;
• R2a means hydrogen, C1-C10 alkyl, C6-C12 aryl or C7-C20 aralkyl, each optionally substituted;
• —(CHO2)ra—C≡C—(CH2)pa—R26a;
• —(CH2)ra—C═C—(CH2)pa—R26a,
• R2b means —(CH2)rb—C≡C—(CH2)pb—R26b, —(CHO2)rb—C═C—(CH2)pb—R26b,
• n means 0 to 5,
• ra, rb are the same or different and mean 0 to 4,
• pa, pb are the same or different and mean 0 to 3,
• R3a means hydrogen or a C1-C10 alkyl, C6-C12 aryl or C7-C20 aralkyl, each optionally substituted,
• R3b means OH or OPG14 where PG14 is a protective group,
• R14 means hydrogen, OR14a or Hal, where R14a is hydrogen, SO2-alkyl, SO2-aryl or SO2-aralkyl,
• R4 means hydrogen, C1-C10 alkyl, C6-C12 aryl or C7-C20 aralkyl, each optionally substituted;
• Hal;
• OR25;
• or CN;
• R25 means hydrogen or a protective group PG5,
• R26a, R26b are the same or different and mean hydrogen;
• C1-C10 alkyl, C6-C12 aryl or C7-C20 aralkyl, each optionally substituted;
• C1-C10 acyl, or, if pa or pb>0, additionally a group OR27,
• R27 means hydrogen or a protective group PG6,
• R5 means hydrogen, C1-C10 alkyl, C6-C12aryl, C7-C20 aralkyl, each optionally substituted;
• or (CH2)s-T,
• whereby
• s stands for 1, 2, 3 or 4,
• T stands for OR22 or Hal,
• R22 stands for hydrogen or a protective group PG4,
• R6, R7 each mean a hydrogen atom, or taken together an additional bond or an oxygen atom,
• G means a group X═CR8— or a bi- or tricyclic aryl radical,
• R8 means hydrogen;
• halogen;
• CN;
• or a C1-C20 alkyl, C6-C12 aryl, C7-C20 aralkyl group each of which can be substituted,
• X means an oxygen atom, two alkoxy groups OR23, a C2-C10-alkylene-α,ω-dioxy group which can be straight-chain or branched, H/OR9 or a grouping CR10R11,
• whereby
• R23 stands for a C1-C20 alkyl radical,
• R9 stands for hydrogen or a protective group PGx,
• R10,R11 are the same or different and stand for hydrogen;
• a C1-C20 alkyl, C6-C12 aryl or C7-C20 aralkyl radical each optionally substituted;
• or R10 and R11 together with the methylene carbon atom jointly stand for a 5- to 7-membered carbocyclic ring,
• D-E means a group —CH2—CH2—, —O—CH2—,
• A-Y means a group O—C(═O), O—CH2, CH2C(═O), NR29—C(═O), or NR29—SO2,
• R29 means hydrogen or C1-C10 alkyl,
• Z means an oxygen atom or H/OR12,
• whereby
• R12 is hydrogen or a protective group PGz,
• Hal means halogen.