CN-122029142-A - Improved process for synthesizing all (E) -heptaisopentenol (C35-OH)

Abstract

The present disclosure relates to an improved method for the regio-and stereospecific synthesis of polyisoprenyl compounds. More particularly, it discloses the regio-and stereospecific synthesis of (2E, 6E,10E,14E,18E, 22E) -3,7,11,15,19,23,27-heptamethyl octacosa-2,6,10,14,18,22,26 heptaen-1-ol useful for the synthesis of vitamin K2-7.

Inventors

• R. Biens
• P. Nippert
• K. KELLER
• P. K. Wola
• MEHTA DEEPA

Assignees

• 辛纳吉亚生命科学私人有限公司

Dates

Publication Date

20260512

Application Date

20241004

Priority Date

20231005

Claims (3)

1. 1. A process for the synthesis of (2E, 6E,10E,14E,18E, 22E) -3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-ol, the process comprising A) Reacting (2E, 6E,10E,14E, 18E) -3,7,11,15,19,23-hexamethyl-9- (phenylsulfonyl) tetracosyl-2, 6,10,14,18, 22-hexaen-1-ol with PCl 3 in dimethylformamide and hexane to obtain 1- ((2E, 6E,10E,14E, 18E) -1-chloro-3,7,11,15,19,23-hexamethyltetracosyl-2, 6,10,14,18, 22-hexaen-9-ylsulfonyl) benzene B) Reacting 1- ((2E, 6E,10E,14E, 18E) -1-chloro-3,7,11,15,19,23-hexamethyltetracos-2, 6,10,14,18, 22-hexa-en-9-ylsulfonyl) benzene with sodium benzene sulfinate in DMF to obtain 1- ((2E, 6E,10E,14E, 18E) -3,7,11,15,19,23-hexamethyl-1- (phenylsulfonyl) tetracos-2, 6,10,14,18, 22-hexa-en-9-ylsulfonyl) benzene C) Reacting 1- ((2E, 6E,10E,14E, 18E) -3,7,11,15,19,23-hexamethyl-1- (phenylsulfonyl) tetracosyl-2, 6,10,14,18, 22-hexa-en-9-ylsulfonyl) benzene with 4-chloroisopentenyl acetate in the presence of potassium tert-butoxide, TBAB/and 18-crown-6 in THF to give (2E, 6E,10E,14E,18E, 22E) -3,7,11,15,19,23,27-heptamethyl-5, 13-bis (phenylsulfonyl) octacos-2,6,10,14,18,22,26-heptaalkenyl acetate D) Hydrolysis of (2E, 6E,10E,14E,18E, 22E) -3,7,11,15,19,23,27-heptamethyl-5, 13-bis (phenylsulfonyl) octacosa-2,6,10,14,18,22,26-heptaalkenylacetate to (2E, 6E,10E,14E,18E, 22E) -3,7,11,15,19,23,27-heptamethyl-5, 13-bis (phenylsulfonyl) octacosa-2,6,10,14,18,22,26-heptaen-1-ol in the presence of KOH and methanol E) Reduction of (2E, 6E,10E,14E,18E, 22E) -3,7,11,15,19,23,27-heptamethyl-5, 13-bis (phenylsulfonyl) octacosa-2,6,10,14,18,22,26-heptaen-1-ol to (2E, 6E,10E,14E,18E, 22E) -3,7,11,15,19,23,27-heptamethyl octacosa-2,6,10,14,18,22,26-heptaen-1-ol in THF in the presence of a superhydrogen compound 。
2. 2.A compound having the formula 1- ((2E, 6E,10E,14E, 18E) -3,7,11,15,19,23-hexamethyl-1- (phenylsulfonyl) tetracosyl-2, 6,10,14,18, 22-hexaen-9-ylsulfonyl) benzene.
3. 3. A compound having the formula (2 E,6e,10e,14e,18e,22 e) -3,7,11,15,19,23,27-heptamethyl-5, 13-bis (phenylsulfonyl) octacosa-2,6,10,14,18,22,26-heptaen-1-ol.

Description

Improved process for synthesizing all (E) -heptaisopentenol (C35-OH) RELATED APPLICATIONS The present application relates to and claims priority from complete application 202321066937 filed on month 5 of 2023 and complete application 202421009595 filed on month 13 of 2024, both of which are incorporated herein in their entireties. Technical Field The present disclosure relates to an improved method for the regio-and stereospecific synthesis of polyisopentenyl compounds (polyprenyl compound). More particularly, it discloses the regio-and stereospecific synthesis of (2E, 6E,10E,14E,18E, 22E) -3,7,11,15,19,23,27-heptamethyl octacosa-2,6,10,14,18,22,26 heptaen-1-ol useful for the synthesis of vitamin K2-7. Background Polyprenol (polyprenol) represents a class of unsaturated acyclic aliphatic alcohols with at least four isoprene units joined head to tail, with the hydroxyl groups attached to the head of the chain. These members differ from each other in terms of their chain length and the stereochemistry of their internal isoprene units. The polyisoprenols are an indispensable constituent of the biological membranes of living cells and are present as free alcohols and/or carboxylic esters thereof. Three types of natural polyisoprenols are (a) all-trans-polyisoprenols, (b) di-trans, poly-cis-isopentenyl or tri-trans, poly-cis-isopentenyl, and (c) di-trans, poly-cis alpha-saturated isopentenyl. Polyprenols are widely found in bacteria, plants, yeasts and fungi. Umbreit et al (J. Bacteriology journal of Bacteriology (1972), 1302-1305) isolated and characterized C5-isopentenol and its derivatives from Streptococcus faecalis (Streptococcus faecalis). Basyuni et al (SYS REV PHARM [ review of pharmaceutical systems ] (2020) 11 (7): 89-97) analyzed the distribution of polyisoprenol in oil palm seed tissue using two-dimensional thin layer chromatography. It is reported that the polyisoprenol is nontoxic, non-mutagenic, non-teratogenic and non-carcinogenic in humans. They exhibit anti-tumor, anti-hepatitis c virus and anti-HIV effects and are used as adjuvants for leukemia chemotherapy and radiotherapy. They are also therapeutic agents for hypertension, high cholesterol, diabetes, gout, lupus and other immune dysfunction, and thus have been widely studied. Substitution of hydroxyl groups has been explored for use in developing anti-tumor and anti-anemia effects as antipsychotics. Isopentenyl acetate exhibits antiulcer and antithrombotic activity. EP 0239 729 B1 discloses injection solutions containing polyisoprenols for enhancing the in vivo use of the polyisoprenols. Polyisopentenol is supplied by Larhodamine Inc. in Sweden (Larodan) and Indofine Inc. in the United states. Drug Ropren (which exhibits brain and liver protection) contains a 95% purity concentrate of polyisopentenol. (Zhang et al Fitoterapia [ phytotherapy ] 106 (2015) 184-193). Solanesol (solanesol) is the first polyisoprenol separated from tobacco leaves with methanol and ether. Solanesol is also isolated from tobacco, mulberry, and silkworm excrement unsaponifiable matter. The polyisoprenol is separated from the contaminants of the cellulose pulp in the paper mill. The isolation, purification, synthesis, structural and functional biological activity correlation, and pharmacology of polyisoprenols and derivatives have been extensively studied and reviewed. Yan et al (phytochem. Rev. [ phytochemical review ] (2015) 14 (3) 403-417) reviewed the resources, derivatives, bioactivity, pharmaceutical use and biosynthesis of solanesol. Although the polyisoprenol is widely distributed in nature, its content in plants is low and the yield is low during the separation and purification processes, resulting in high recovery costs. Muramatsu et al (J.biosci. And bioengg. [ journal of bioscience and bioengineering ] 106 (3) 263-267 (2008)), J.biosci. And bioengg. [ journal of bioscience and bioengineering ] (108) (1) 52-55 (2009)) describe microbial production of farnesol (farnesol) and related isopentenol. In view of the variety of applications of polyisoprenols and their importance in the synthesis of isoprenoid quinones of biological importance and the limited occurrence in nature, efforts have been made for the synthesis of polyisoprenols, in particular all-trans polyisoprenols. Cheng and Loh (Pure appl. Chem. [ Pure chemical and applied chemistry ], 77, (7) 1199-1206, 2005.) disclose asymmetric alpha-prenylation of various aldehydes to give the corresponding alpha-isopentenol. The stereoselective synthesis of solanesol and all-trans-decaprenol is reported by Sato et al (J Chem Soc Perkin I [ British chemical society of Fabry-Perot I ] (1981) 761). Altman et al (J. Am. Chem. Soc. [ American society of chemistry ], 1972, 94, 3257; synthesis [ Synthesis ], 1974, 129) report the synthesis of all-trans-geranylgeraniol. Masaki et al (Tetrahedron Lett. [ Tetrahedron flash ] (1978), 4539, J. Chern. Soc., [ British chemical society, chemical communications ], (1979), 855;Te