Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2000-12-15
2002-12-17
Padmanabhan, Sreeni (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S379000, C568S591000, C568S673000, C568S838000, C560S121000, C562S503000, C549S436000
Reexamination Certificate
active
06495725
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a novel optically active enone derivative, which is a useful intermediate for natural products such as prostagrandins and drugs, processes for the preparation thereof and a novel optically active compound as intermediates.
BACKGROUND OF THE INVENTION
Recently, chiral alcohols with a plurality of hydroxyl groups have found wide and versatile utility as both enantiomers in the synthesis of optically active natural products or drugs and have become a focus of interest. In particular, the hydroxyl-protected enone form, i.e., 7,7-dimethyl-6,8-dioxabicyclo[3,3,0]oct-3-en-2-one, has been used as important building blocks for the synthesis of a variety of physiologically active substances such as prostagrandins.
Johnson et al. have accomplished a total synthesis of prostagrandin E
2
from optically active 7,7-dimethyl-6,8-dioxabicyclo[3,3,0]oct-3-en-2-one (J. Am. Chem. Soc., 1986, 108, 5655). According to this process, the optically active enone was synthesized by optical resolution of the racemate with (+)-N,S-dimethyl-S-phenylsulfoximine. However, imine as a resolving agent is expensive, and the resolution according to the process should be made after addition of imine by conducting the reaction at a low temperature of −78° C. Moreover, the process requires a reaction to regenerate a carbonyl group after resolution, which cannot always be easily carried out in an industrial scale. Thus, there has been a demand for a more simplified and convenient process for the preparation of an optically active enone, such as 7,7-dimethyl-6,8-dioxabicyclo[3,3,0]oct-3-en-2-one.
SUMMARY OF THE INVENTION
An object of the invention is to provide a more simplified process for the preparation of an optically active enone, such as 7,7-dimethyl-6,8-dioxabicyclo[3,3,0]-oct-3-en-2-one.
Another object of the invention is to provide intermediates obtainable during the process according to the invention.
Further object of the invention is to provide a novel optically active enone.
DETAILED DESCRIPTION OF THE INVENTION
We have found a simplified and efficient process for the preparation of both enantiomers of an optically active enone, for example, 7,7-dimethyl-6,8-dioxabicyclo[3,3,0]oct-3-ene-2-one, starting an optically active alcohol derivative represented by the formula (9).
wherein R
1
, R
4
and R
5
are as defined below.
Moreover, we have found that the intermediate obtained in the said process is a novel optically active compound, which is also useful chiral building blocks like the end product, i.e., optically active enone. The invention has been completed upon the above findings.
More specifically, as illustrated in Scheme 1 below, the present invention provides a process for the preparation of an optically active enone represented by the formula (4), which comprises steps of (A) deprotecting the protecting group for the hydroxyl group at the 1-position in a compound represented by the formula (1) to a hydroxyl group (compound (2)), (B) oxidizing the hydroxyl group to a ketone group (compound (3)) and (C) deprotecting the protecting group for the hydroxyl group at the 4-position to form a double bond between the carbon atom at the 4-position and the carbon atom at the 5-position to prepare the desired enone. Here all chemical names are referred to in accordance with the IUPAC nomenclature. For convenience sake, however, the position of a functional group shall be represented in accordance with the numbering as shown in the formula (1).
wherein R
1
and R
4
independently represent a cumyl group, &agr;,&agr;-diethylbenzyl, &agr;,&agr;-dimethyl-p-methoxybenzyl, t-butyldimethylsilyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, isopropyldimethylsilyl or ethyldimethylsilyl, R
2
and R
3
jointly represent acetonide, methyl ethyl ketal or diethyl ketal, and R
5
represents a hydrogen atom, an alkyl group having not more than 20 carbon atoms or a phenyl group.
Also, as illustrated in Scheme 2 below, the invention provides a process for the preparation of an optically active enone represented by the formula (7), which comprises the steps of (A′) deprotecting the protecting group for the hydroxyl group at the 4-position in a compound represented by the formula (1) to a hydroxyl group (compound (5)), (B′) oxidizing the hydroxyl group to a ketone group (compound (6)) and (C′) deprotecting the protecting group for the hydroxyl group at the 1-position to form a double bond between the carbon atom at the 1-position and the carbon atom at the 5-position to prepare the desired enone.
wherein R
1
, R
2
, R
3
, R
4
and R
5
are as defined above.
Further, as illustrated in Scheme 3 below, the invention provides a process for the preparation of an optically active enone represented by the formula (13), which comprises the steps of deprotecting the protecting group for the hydroxyl group at the 1-position in a compound represented by the formula (10) wherein the protecting group at the 1-position is a cumyl group and the protecting groups at the 2- and 3-positions are acetonide to a hydroxyl group (compound (11)); oxidizing the hydroxyl group to a ketone group (compound (12)); and deprotecting the protecting group for the hydroxyl group at the 4-position to form a double bond between the carbon atom at the 4-position and the carbon atom at the 5-position to prepare the desired enone.
wherein R
4
and R
5
are as defined above.
Further, as illustrated in Scheme 4 below, the invention provides a process for the preparation of an optically active enone represented by the formula (16), which comprises the steps of deprotecting the protecting group for the hydroxyl group at the 4-position in a compound represented by the formula (10) wherein the protecting group at the 1-position is a cumyl group and the protecting groups at the 2- and 3-positions are acetonide to a hydroxyl group (compound (14)); oxidizing the hydroxyl group to a ketone group (compound (15)); and deprotecting the protecting group for the hydroxyl group at the 1-position to form a double bond between the carbon atom at the 1-position and the carbon atom at the 5-position to prepare the desired enone.
wherein R
4
and R
5
are as defined above.
Moreover, as illustrated in Scheme 5 below, the invention provides a process for the preparation of an optically active enone represented by the formula (16), which comprises the steps of deprotecting the protecting group for the hydroxyl group at the 4-position in a compound represented by the formula (17) wherein the protecting group at the 4-position is a cumyl group and the protecting groups at the 2- and 3-positions are acetonide to a hydroxyl group (compound (18)); oxidizing the hydroxyl group to a ketone group (compound (19)); and deprotecting the protecting group for the hydroxyl group at the 1-position to form a double bond between the carbon atom at the 1-position and the carbon atom at the 5-position to prepare the desired enone.
wherein R
1
and R
5
are as defined above.
Also, as illustrated in Scheme 6 below, the invention provides a process for the preparation of an optically active enone represented by the formula (13), which comprises the steps of deprotecting the protecting group for the hydroxyl group at the 1-position in a compound represented by the formula (17) wherein the protecting group at the 4-position is a cumyl group and the protecting groups at the 2- and 3-positions are acetonide to a hydroxyl group (compound (20)); oxidizing the hydroxyl group to a ketone group (compound (21)); and deprotecting the protecting group for the hydroxyl group at the 4-position to form a double bond between the carbon atom at the 4-position and the carbon atom at the 5-position to prepare the desired enone.
wherein R
1
and R
5
are as defined above.
Still further, the invention provides an optically active compound represented by the formula (1). The compounds represented by the formula (1) include enantiomers thereof.
The invention also provides optically active compoun
Chisso Corporation
Padmanabhan Sreeni
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