183433-75-2

Upstream product

• 108-05-4 vinyl acetate 
• 183433-74-1 5-Benzyloxymethyl-4-(1-hydroxy-1-hydroxymethyl-propyl)-6-methoxy-pyridine-2-carboxylic acid propyl ester 
• 108-22-5 Isopropenyl acetate 
• 183433-68-3 5-Benzyloxymethyl-4-(2-ethyl-[1,3]dioxolan-2-yl)-6-methoxy-pyridine-2-carboxylic acid propyl ester 
• 183433-72-9 5-Benzyloxymethyl-6-methoxy-4-(1-methylene-propyl)-pyridine-2-carboxylic acid propyl ester 
• 183433-67-2 3-Benzyloxymethyl-6-chloro-4-(2-ethyl-[1,3]dioxolan-2-yl)-2-methoxy-pyridine 
• 183433-66-1 [6-Chloro-4-(2-ethyl-[1,3]dioxolan-2-yl)-2-methoxy-pyridin-3-yl]-methanol 
• 183433-65-0 6-Chloro-4-(2-ethyl-[1,3]dioxolan-2-yl)-2-methoxy-pyridine-3-carbaldehyde 
• 183433-64-9 6-chloro-4-(2-ethyl-1,3-dioxolan-2-yl)-2-methoxypyridine 
• 183433-63-8 2,6-dichloro-4-(2-ethyl-1,3-dioxolan-2-yl)pyridine 
• 183433-62-7 1-(2,6-dichloropyridin-4-yl)propan-1-one 
• 5398-44-7 2,6-dichloropyridine-4-carboxylic acid 
• 99-11-6 citrazinic acid 

Downstream Products

• 183433-96-7 5-Benzyloxymethyl-4-((S)-1-formyl-1-hydroxy-propyl)-6-methoxy-pyridine-2-carboxylic acid propyl ester 
• 183434-02-8 propyl (S)-4-ethyl-3,4,7,8-tetrahydro-4-hydroxy-3,8-dioxo-1H-pyrano[3,4-c] pyridine-6-carboxylate 
• 97682-44-5 irinotecan 
• 86639-52-3 7-ethyl-10-hydroxycamptothecin 
• 110351-94-5 (4S)-4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione 

Relevant academic research and scientific papers

Practical asymmetric synthesis of (S)-4,ethyl-7,8-dihydro-4-hydroxy-1H- pyrano[3,4-f]indolizine-3,6,10(4H)-trione, a key intermediate for the synthesis of Irinotecan and other camptothecin analogs

A practical asymmetric synthesis of (S) 4-ethyl-7,8-dihydro-4-hydroxy- 1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6- methoxypyridine 5. An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine (6) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert (S)-16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.

Application of immobilized lipase in production of camptosar (CPT-11)

Lipase from Pseudomonas cepaica (Amano, PS-30) was immobilized on celite and used in organic solvent for the selective acylation of a key alcohol intermediate. The compound was transformed in the synthesis to the anticancer drug Camptosar (CPT-11). Catalyst activity was influenced by the water content and method used to dry the catalyst. This resolution has been conducted on production scale with equal weight of recyclable catalyst.