Process for preparation of calcitriol lactone and related intermediates
First Claim
Patent Images
1. A process for synthesizing diastereoisomers a, b, c or d of a compound of the formula ##STR5## wherein in diastereoisomer a, X═
- H;
W═
Z═
OH; and
Y═
H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;
in diastereoisomer b, X═
Z═
OH;
W═
H; and
Y═
H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;
in diastereoisomer c, X═
Y═
OH;
W═
H; and
Z═
H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;
in diastereoisomer d, W=Y=OH;
X=H; and
Z=H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;
which comprises the steps of;
(a) protecting the hydroxyl group of enantiomerically pure glycidol or 2-alkylglycidol with a suitable first protective group;
(b) reductively cleaving the protected product of step (a) with an aromatic radical anion;
(c) reacting the cleaved product of step (b) with De-A,B-8β
-hydroxy-24-nor-cholan-23-al which has had its hydroxyl group protected with a suitable second protective group to form epimeric hydrindane diols;
(d) removing the first protective group from the hydrindane diol product of step (c) to yield an epimeric mixture of hydrindane triols;
(e) separating the epimeric hydrindane triol isomers of step (d); and
(f) removing the second protective group from the separated epimeric hydrindane triol isomers of step (e) to yield hydrindane tetrols.
1 Assignment
0 Petitions
Accused Products
Abstract
A process for synthesizing (23S,25R)-calcitriol lactone and related Vitamin D analogs comprises reacting protected enantiomerically pure glycidol or 2-alkylglycidol with protected De-A,B-8β-hydroxy-24-nor-cholan-23-al, removing the protective groups from the epimeric product mixture and separating the epimers, to give a hydrindane tetrol product, followed by oxidation and protection of the hydrindane tetrol product, reacting the tetrol product with the lithium salt of (3S)-(3α,5β,Z)-2-(2-methylene-3,5-bis-((1,1-dimethylethyl)dimethylsilyloxy)cyclohexylidene)ethyl diphenyl phosphine oxide and removing the final protective groups. Certain intermediate compounds also show biological activity as angiostatic agents.
4 Citations
17 Claims
-
1. A process for synthesizing diastereoisomers a, b, c or d of a compound of the formula ##STR5## wherein in diastereoisomer a, X═
- H;
W═
Z═
OH; and
Y═
H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;in diastereoisomer b, X═
Z═
OH;
W═
H; and
Y═
H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;in diastereoisomer c, X═
Y═
OH;
W═
H; and
Z═
H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;in diastereoisomer d, W=Y=OH;
X=H; and
Z=H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;which comprises the steps of; (a) protecting the hydroxyl group of enantiomerically pure glycidol or 2-alkylglycidol with a suitable first protective group; (b) reductively cleaving the protected product of step (a) with an aromatic radical anion; (c) reacting the cleaved product of step (b) with De-A,B-8β
-hydroxy-24-nor-cholan-23-al which has had its hydroxyl group protected with a suitable second protective group to form epimeric hydrindane diols;(d) removing the first protective group from the hydrindane diol product of step (c) to yield an epimeric mixture of hydrindane triols; (e) separating the epimeric hydrindane triol isomers of step (d); and (f) removing the second protective group from the separated epimeric hydrindane triol isomers of step (e) to yield hydrindane tetrols. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
- H;
-
10. A process for synthesizing diastereoisomers a, b, c or d of a compound of the formula ##STR6## wherein in diastereoisomer a, X═
- H;
W═
Z═
OH; and
Y═
H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;in diastereoisomer b, X═
Z═
OH;
W═
H; and
Y═
H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;in diastereoisomer c, X═
Y═
OH;
W═
H; and
Z═
H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;in diastereoisomer d, W═
Y═
OH;
X═
H; and
Z═
H, C1 -C6 alkyl, branched alkyl or cycloalkyl, saturated or unsaturated;which comprises the steps of; (a) protecting the hydroxyl group of enantiomerically pure glycidol or 2-alkylglycidol with a suitable first protective group; (b) reductively cleaving the protected product of step (a) with an aromatic radical anion; (c) reacting the cleaved product of step (b) with De-A,B-8β
-hydroxy-24-nor-cholan-23-al which has had its hydroxyl group protected with a suitable second protective group to form epimeric hydrindane diols;(d) removing the first protective group from the hydrindane diol product of step (c) to yield an epimeric mixture of hydrindane trioIs; (e) removing the second protective group from the epimeric hydrindane triol isomers of step (d) to yield hydrindane tetrols; and (f) separating the epimeric hydrindane tetrol isomers. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17)
- H;
Specification
-
- Resources
Litigation Campaign Assessment
Thank you for your request. You will receive a custom alert email when the Litigation Campaign Assessment is available.
×
-
Current AssigneeAlcon Manufacturing Limited (Alcon Incorporated)
-
Original AssigneeAlcon Laboratories Incorporated (Alcon Incorporated)
-
InventorsConrow, Raymond E.
-
Primary Examiner(s)Ivy, C. Warren
-
Assistant Examiner(s)OWENS, AMELIA A
-
Application NumberUS08/273,387Time in Patent Office456 DaysField of Search568/819US Class Current568/819CPC Class CodesC07B 2200/07 Optical isomersC07C 2602/24 the ring system containing ...C07C 29/132 by reduction of an oxygen c...C07C 35/32 the condensed ring system b...C07D 307/33 in position 2, the oxygen a...Y02P 20/55 Design of synthesis routes,...
