US 12,084,699 B2
Solid form of (−)-Ambrox formed by a bioconversion of homofarnesol in the presence of a biocatalyst
Ghislain Sanhaji, Warmeriville (FR); Alix Rousseaux, Verzenay (FR); Sandrine Noel, Warmeriville (FR); and Eric Eichhorn, Zurich (CH)
Assigned to Givaudan SA, Vernier (CH)
Filed by Givaudan SA, Vernier (CH)
Filed on May 23, 2023, as Appl. No. 18/322,167.
Application 18/322,167 is a continuation of application No. 17/680,840, filed on Feb. 25, 2022, granted, now 11,773,419.
Application 17/680,840 is a continuation of application No. 17/070,385, filed on Oct. 14, 2020, granted, now 11,401,541, issued on Aug. 2, 2022.
Application 17/070,385 is a continuation of application No. 16/095,444, granted, now 10,844,412, issued on Nov. 24, 2020, previously published as PCT/EP2017/059327, filed on Apr. 20, 2017.
Claims priority of application No. PCT/EP2016/058987 (WO), filed on Apr. 22, 2016; application No. PCT/EP2016/058997 (WO), filed on Apr. 22, 2016; and application No. 1618090 (GB), filed on Oct. 26, 2016.
Prior Publication US 2023/0357809 A1, Nov. 9, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12P 17/04 (2006.01); A61Q 13/00 (2006.01); C07D 307/92 (2006.01)
CPC C12P 17/04 (2013.01) [A61Q 13/00 (2013.01); C07D 307/92 (2013.01); C07B 2200/07 (2013.01); C07B 2200/13 (2013.01); C12Y 504/99017 (2013.01)] 15 Claims
OG exemplary drawing
 
1. A method of preparing a solid form of (−)-Ambrox of formula (I)

OG Complex Work Unit Chemistry
wherein the solid form of (−)-Ambrox is formed by a bioconversion process; said method comprising the steps of:
I) forming crystalline (−)-Ambrox in a bioconversion medium by means of a biocatalytic process;
II) separating the crystalline (−)-Ambrox from the bioconversion medium;
wherein the bioconversion medium obtained from the bioconversion process comprises a solid phase containing crude (−)-Ambrox, a liquid phase or phases consisting of water and an oily phase containing residual homofarnesol and other oily or oil-soluble impurities or by-products (II), (III) and (IV) present in the oily phase;

OG Complex Work Unit Chemistry
wherein the bioconversion process is an enzyme-catalyzed cyclization of homofarnesol comprising a mixture of 7E,3E and 7E,3Z isomers of homofarnesol wherein the cyclization reaction is carried out in the presence of an SHC biocatalyst capable of bioconverting a homofarnesol mixture enriched in the 7E,3E isomer to (−)-Ambrox, wherein in the presence of appreciable amounts of homofarnesol, (−)-Ambrox and the by-products remain dissolved together; and wherein a reduction in the level of unreacted homofarnesol in admixture with (−)-Ambrox and the compounds (II), (III) and (IV) results in crystallization of (−)-Ambrox and facilitates downstream processing and isolation and/or purification of (−)-Ambrox in a solid form from the bioconversion medium.