Synthesis of a Fragment A Derivative of an Antibiotic, Nosiheptide

Abstract

Two 4-ethoxycarbonyl thiazolyl groups were introduced into 2- and 5-positions of 3-hydroxypyridine in 8 steps using 5-cyano-3-hydroxypyridine (2) as the starting material. The pyridine derivative obtained in the last step was converted to a fragment A derivative (21) by stepwise introduction of the 2-substituted 4-thiazolyl group into the 6-position. The total yield for the formation of 21 via 14 steps was 7.6%.

Catalytic Asymmetric Baeyer–Villiger Oxidation in Water by Using PtII Catalysts and Hydrogen Peroxide: Supramolecular Control of Enantioselectivity

“…Shin and co‐workers have published the results of extensive research relating to the synthesis of the central pyridine cores of many different thiopeptide antibiotics, for example A10255,60 berninamycin,61 cyclothiazomycin,54, 62, 63 GE2270A,49, 64, 65 micrococcin P,66 nosiheptide,67, 68 and thiocilline I 69. There are a number of common strategies applied in these syntheses as illustrated in the routes to the substituted pyridines of nosiheptide ( 6 , Scheme ) and GE2270A ( 5 , Scheme ).…”

From Amino Acids to Heteroaromatics—Thiopeptide Antibiotics, Nature's Heterocyclic Peptides

“…This could subsequently be converted into thiazole 35 under classical Hantzsch conditions, and hence afford berninamycinic acid (36, Scheme 10). [59] Shin and co-workers have published the results of extensive research relating to the synthesis of the central pyridine cores of many different thiopeptide antibiotics, for example A10255, [60] berninamycin, [61] cyclothiazomycin, [54,62,63] GE2270A, [49,64,65] micrococcin P, [66] nosiheptide, [67,68] and thiocilline I. [69] There are a number of common strategies applied in these syntheses as illustrated in the routes to the substituted pyridines of nosiheptide (6, Scheme 11) and GE2270A (5, Scheme 12).…”

“…This four-step procedure involves formation of triflate 41, a Stille cross-coupling, followed by reaction with NBS to give bromoketone 42, and lastly a Hantzsch reaction to give the desired thiazole moiety in pyridine 43. [67,68] However, to use this pyridine in a total synthesis of nosihep- tide, one would have to differentiate the two ethyl ester groups, and effect the required orthogonal deprotection.…”

Von Aminosäuren zu Heteroarenen – Thiopeptid‐Antibiotika als heterocyclische Peptide aus der Natur

“…synthetisierten die Pyridinkerne vieler unterschiedlicher Thiopeptid‐Antibiotika. Beispiele sind die Synthesen von A10255,60 Berninamycin,61 Cyclothiazomycin,54, 62, 63 GE2270A,49, 64, 65 Micrococcin P,66 Nosiheptid67, 68 und Thiocillin I 69. Die Synthesen erfolgten nach gängigen Methoden, die in den Schemata und am Beispiel der substituierten Pyridineinheiten von Nosiheptid ( 6 ) bzw.…”

“…Bei Reaktion mit NBS entsteht das Bromketon 42 , das schließlich durch eine Hantzsch‐Reaktion die gewünschte Thiazoleinheit unter Entstehung des Pyridins 43 liefert 67. 68 Um jedoch dieses Pyridin bei einer Totalsynthese von Nosiheptid verwenden zu können, müsste man die beiden Ethylesterfunktionen noch differenzieren und die Schutzgruppen orthogonal wieder abspalten.…”