Efficient and scalable total synthesis of calcitroic acid and its ¹³C-labeled derivative

Abstract

Calcitroic acid and its 13C labeled derivative has been synthesized from Inhoffen-Lythgoe diol in 11 steps with an overall yield of 21%.

Calcitroic Acid–A Review

“…Very recently, a synthesis using commercially available chemicals was reported, that for the first time enabled the synthesis of gram quantities of calcitroic acid (Scheme 5). 47 …”

“…One important factor impeding calcitroic acid research has been the unavailability of this compound. Hopefully, this will be overcome with the recently published new method from Meyer, et al 47 Even the older synthetic methods might inspire chemists to develop alternative new syntheses. A great deal of knowledge as gained on the metabolic formation of calcitroic acid using recombinant enzymes with further detail on their cofactors and enzyme kinetics.…”

Rh(III)-Catalyzed Enaminone-Directed C–H Coupling with α-Diazo-α-phosphonoacetate for Reactivity Discovery: Fluoride-Mediated Dephosphonation for C–C Coupling Reactions

“…Organophosphorus compounds are useful synthons for diverse types of chemical transformations . Notable synthetic achievements include Wittig reaction (phosphonium ylide), Horner reaction (phosphine oxide), Wadsworth–Emmons reaction (phosphonate), and Seyferth–Gilbert reaction (diazophosphonate). These reactions are driven by the high oxophilic reactivity of a phosphorus atom and typically require the use of a strong base for deprotonation generation of nucleophilic carbanion.…”

Synthesis of 13C‐labelled cutin and suberin monomeric dicarboxylic acids of the general formula HO213C‐(CH2)n‐13CO2H (n = 10, 12, 14, 16, 18, 20, 22, 24, 26, 28)

“…[47][48][49] The use of K 13 CN therefore is the obvious choice especially in the synthesis of labelled carboxylic acids, which also been pointed out for the synthesis of labelled calcitroic acid. 50 So the synthesis of 1,12-dodecanedioic acid, 3a, and 1,14-tetradecanedioic acid, 3b, quite straightforward works starting from the corresponding α,ω-dibromoalkanes with two carbon atoms less compared with the desired products. Therefore, the reaction of 1,10-dibromodecane, 1a, or 1,12-dibromododecane, 1b, with K 13 CN yields the corresponding dinitriles 2a and 2b, which then might be hydrolyzed to produce the labelled dicarboxylic acids 3a and 3b in high overall yields (Scheme 1).…”