US2008161580A1PendingUtilityA1
Protected 3,5-dihydroxy-2,2-dimethyl-valeroamides for the synthesis of epothilones and derivatives and process for the production and the use
Est. expiryAug 3, 2021(expired)· nominal 20-yr term from priority
C07D 493/04C07F 7/1892C07C 235/16C07F 7/1804C07D 319/06C07C 235/06C07D 319/08
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Claims
Abstract
The invention relates to new protected 3,5-dihydroxy-2,2-dimethyl-valeroamides for the synthesis of epothilones and derivatives and process for the production and the use of the new compounds for the production of epothilones or epothilone derivatives.
Claims
exact text as granted — not AI-modified1 .- 32 . (canceled)
33 . A method for producing a natural or synthetic epothilone compound or derivative thereof, which comprises reacting a compound of following formula (I) as a starting material in at least one step in the method:
in which
R 1 and R 2 are the same or different and, independently of one another, stand for an alcohol protective group or,
R 1 and R 2 are bridged and together stand for a ketal protective group, and
Y stands for a group —NA1A2, whereby A1 and A2, independently of one another, stand for C 1 -C 6 alkyl, aryl, aralkyl, —OH, —OMe, or —O-benzyl,
or Y stands for
where the dashed line bonds indicate the point of attachment.
34 . The method of claim 33 , wherein the alcohol protective groups are selected from: benzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, THP, TBDMS, TMS, TES, TIP, TBDPS, MEM, MOM, allyl and trityl groups; and the ketal protective group is selected from groups of the following formulae:
where the dashed line bonds indicate the points of attachment.
35 . The method of claim 33 , wherein, for A1 and A2, aryl is phenyl and aralkyl is benzyl.
36 . A process for producing a compound of the following formula (I):
in which
R 1 and R 2 are the same or different and, independently of one another, stand for an alcohol protective group or,
R 1 and R 2 are bridged and together stand for a ketal protective group, and
Y stands for a group —NA1A2, whereby A1 and A2, independently of one another, stand for C 1 -C 6 alkyl, aryl, aralkyl, —OH, —OMe, or —O-benzyl,
or Y stands for
where the dashed line bonds indicate the point of attachment;
which process comprises protecting a corresponding compound having free alcohol groups in place of OR 1 and/or OR 2 with an alcohol protective group R 1 and/or R 2 or a ketal protective group of R 1 and R 2 together.
37 . A process of claim 36 , wherein protective groups R 1 and R 2 are both a TBDMS group or are, together, an acetone ketal group.
38 . A method for producing a natural or synthetic epothilone compound or a derivative thereof, which comprises reacting a compound of the following formula (II) as a starting material in at least one step in the method of producing:
in which Y stands for a group —NA1A2, where A1 and A2, independently of one another, stand for C 1 -C 6 alkyl, aryl, aralkyl, —OH, —OMe, or —O-benzyl,
or Y is
where the dashed line bonds indicate the point of attachment.
39 . The method of claim 38 , wherein, for A1 and A2, aryl is phenyl and aralkyl is benzyl.
40 . A method for producing a natural or synthetic epothilone compound or a derivative thereof, which comprises reacting a compound of the following formula (III) as a starting material in at least one step in the method of producing:
in which R 1 stands for an alcohol protective group, and
Y stands for a group —NA1A2, where A1 and A2, independently of one another, stands for C 1 -C 6 alkyl, aryl, aralkyl, —OH, —OMe, or —O-benzyl,
or Y is
where the dashed line bonds indicate the point of attachment.
41 . A method of claim 40 , wherein the alcohol protective group is selected from: benzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, THP, TBDMS, TMS, TES, TIP, TBDPS, MEM, MOM, allyl and trityl groups.
42 . A method of claim 40 , wherein for A1 and A2, aryl is phenyl and aralkyl is benzyl.
43 . A process for producing an optically active compound of the following formula (III) wherein the configuration at the C-atom of the secondary alcohol is S:
in which R 1 stands for an alcohol protective group, and
Y stands for a group —NA1A2, where A1 and A2, independently of one another, stand for C1-C6 alkyl, aryl, aralkyl, —OH, —OMe, or —O-benzyl,
or Y is
and, where the dashed line bonds indicate the point of attachment,
which process comprises:
chirally reducing the keto group of a compound of formula VII,
whereby radicals R 1 and Y have the above meaning.
44 . The process of claim 43 , wherein the chiral reduction of the keto group is made by catalytic hydrogenation with a Noyori-type catalyst.
45 . The process of claim 43 , wherein the chiral reduction of the keto group is made by enzymatic reaction.
46 . The compound N,N-dimethyl-(5-benzyloxy-2,2-dimethyl-3(S)-hydroxy-pentanoic acid)amide of the formula:
47 . A compound of formula XII:
in which Y stands for a group —NA1A2, where A1 and A2, independently of one another,
stand for C1-C6 alkyl, aryl, aralkyl, —OH, —OMe, or —O-benzyl,
or Y is
where the dashed line bonds indicate the point of attachment, and,
R4 stands for a C 1 -C 6 alkyl, phenyl or benzyl group.
48 . A compound of claim 47 , wherein the configuration at the C-atom of the secondary alcohol is R.
49 . A method for producing a natural or synthetic epothilone or derivative thereof, which comprises reacting a compound of formula XII of claim 47 as a starting material in at least one step in the method of producing.
50 . A process for producing a ketone of formula A
in which
R 1 and R 2 are the same or different and, independently of one another, stand for an alcohol protective group or,
R 1 and R 2 are bridged and together stand for a ketal protective group, and
V stands for a C 1 -C 5 alkyl or alkenyl radical,
which comprises:
reacting a compound of formula Ia
where R 1 and R 2 have the above meanings and
Y stands for a group —NA1A2, whereby A1 and A2, independently of one another, stand for C 1 -C 6 alkyl, aryl, aralkyl, —OH, —OMe, or —O-benzyl,
or Y is
where the dashed line bonds indicate the point of attachment,
with a compound of formula B
M-V (B)
in which M is Li, MgCl, MgBr, or MgI,
and then working up the product under aqueous hydrolysis.
51 . The process of claim 50 , wherein the compound of formula B is MeLi, EtLi, propyl-Li, BuLi, or CH 2 ═CH—CH 2 CH 2 —Li.Join the waitlist — get patent alerts
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