Improved Process for Pilot-Scale Synthesis of Danshensu ((±)-DSS) and Its Enantiomer Derivatives

Abstract

A pilot-scale process has been developed for green and scalable synthesis of (±)-β-(3,4-dihydroxy­phenyl) lactic acid ((±)-DSS) and their two important derivatives, namely, (±)-IDHP [(±)-iso­propyl 2-hydroxy-3-(3,4-di­hydroxy­phenyl)propano­ate] and (±)-DBZ [(±)-bornyl 2-hydroxy-3-(3,4-di­hydroxy­phenyl)propano­ate]. Subsequent hydrogenation has been carried out by employing Raney Ni as catalyst. The improved process results in higher yields of 47.5% for (±)-DBZ and 49.2% for (±)-IDHP compared to the initial process with a yield of 12% for (±)-DBZ and 18% for (±)-IDHP in our original medicinal chemistry route. Furthermore, kilograms of optical DBZ [(−)-S-DBZ and (+)-R-DBZ, >99% ee] and IDHP [(−)-S-IDHP and (+)-R-IDHP, >99% ee] have been produced by chiral high-performance liquid chromatography in good yield (>84%).

Tanshinol borneol ester, a novel synthetic small molecule angiogenesis stimulator inspired by botanical formulations for angina pectoris

“…( S )‐DBZ and ( R )‐DBZ (United States patent no. 8017786) were synthesized by us, using the method described by Bai et al (). Other chemicals were all obtained from Sigma‐Aldrich unless otherwise specified.…”

Reducing 3,4-dihydroxyphenylpyruvic acid tod-3,4-dihydroxyphenyllactic acid via a coenzyme nonspecificd-lactate dehydrogenase fromLactobacillus reuteri

“…DPA was synthesized from treating 3,4‐dihydroxylbenzaldehyde with N ‐acetylglycine at a low cost in our previous work (Bai et al . ). The d ‐DSS production cost of raw materials, cells and separation would be below $100 per kg.…”

“…These promising applications of d ‐DSS stimulated many efforts to develop synthesis strategies (Bai et al . ; Sidoryk et al . ).…”

“…Production of optically pure D-DSS has stimulated interest among researchers in recent years due to its potential for pharmacological applications. D-DSS and its derivatives have anti-oxidant, anti-thrombosis, anti-inflammatory, hypolipidemic, anti-atherosclerosis, hepatoprotective and anti-tumor potential pharmacological activities, as well as the ability to improve microcirculation and immunity and prevent organ damage (Cao et al 2009;Bai et al 2014;Yang et al 2015).…”

“…These promising applications of D-DSS stimulated many efforts to develop synthesis strategies (Bai et al 2014;Sidoryk et al 2018). Enzyme biotransformation is an important method to produce valuable components (France et al 2017).…”