80721-47-7

The invention discloses a synthetic method of pyrroloquinoline quinone. The synthetic method comprises the following steps: carrying out alkali treatment on 2-methoxy-5-nitroaniline hydrochloride as a raw material, so as to obtain a compound 1; carrying out formylation on the compound 1 under a catalysis condition of an ionic liquid, so as to obtain a compound 2; adopting sodium borohydride to reduce the compound 2 to obtain a compound 3; carrying out diazotization on the compound 3, and then enabling action between the diazotized compound 3 and HBF4 to obtain a compound 4; enabling reaction of the compound 4 and 2-methylethyl acetoacetate to obtain a compound 5; treating the compound 5 with formic acid to obtain a compound 6; carrying out amid catalysis and exchange with the ionic liquid on the compound 6 to obtain a compound 7; enabling reaction of the compound 7 and 2-oxodimethyl glutaconate to obtain a compound 8; feeding hydrogen chloride to the compound 8 under the action of Cu(OAc)2*2H2O to obtain a compound 9; carrying out basic hydrolysis on the compound 9 to obtain a compound 10. The synthetic method disclosed by the invention is cheap and accessible in raw materials, stable, high in reaction yield, quick in reaction, and easy for product separation, and is environment-friendly as the catalyst can be recycled.

The invention relates to a novel nine step process for synthesizing PQQ (methoxatin). This process is efficient and reliably provides PQQ in excellent purity and high yield.

The improvement of the PQQ synthesis according to the method of Corey and Tramontano allows the preparation of the triester of this cofactor in the kg scale with an overall yield of 13percent (average 78percent per step), without a bottleneck in the sequence and with crystalline, analytically pure intermediates.The new purification of free PQQ from conc.H2SO4 is remarkable with respect to the application as well as to the stability of this natural product.

Electron-rich methoxyarenes were oxidized with high yields (55-100percent) and under mild conditions to the corresponding paraquinones by magnesium monoperoxyphthalate in the presence of catalytic amounts of a water-soluble iron porphyrin; the reaction was used to prepare methoxatin.

A convergent total synthesis of the novel coenzyme methoxatin (1) is described.This coenzyme is a pyrroloquinoline quinone tailored for efficient oxidation of methanol and formaldehyde in methylotropic bacteria.The synthesis was achieved by joining pyrrole subunit 5a with uvitonic acid ester 8b followed by photocyclization of the resulting olefin 9 to deoxymethoxatin 10.Conversion of 10 to methoxatin proceeded in five steps and led to some elaboration of the chemistry of the unusual pyrroloquinoline heterocycle.The overall yield is ca. 15 percent in 11 operations.

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We report a convergent total synthesis of the coenzyme methoxatin (1) by linking pyrrole subunit (3) with uvitonic acid derivative 4d and oxidative photocyclization to deoxymethoxatin triester 6, followed by seven refunctionalization steps to 1.