Total synthesis of (−)-Allosamidin, an insect chitinase inhibitor, employing chitin as a key starting material

Natural product family 18 chitinase inhibitors

“…Trost's synthesis of 2 also paved the way for a total synthesis of 1, achieved in collaboration with the group of Vasella. 62,63 This employs a more conventional, but nonetheless innovative solution to the problem of generating the unusual allosamine stereochemistry, which has been paralleled in subsequent total syntheses described by Kuzuhara et al 75,76 and Ferrier et al 51 The well-known trichloroacetimidate methodology of Schmidt and Kinzy 77 was employed for the key glycosylation steps. Preparation of the disaccharide moiety was achieved in a convergent fashion from D-glucosamine.…”

“…The preparation of 2 by Kuzuhara et al 85 (Scheme 10) not only established the absolute configuration of the latter, but also formed part of a further total synthesis 75 68 provided the substrate 69 for the projected ring contraction step, which was cleverly carried out with the basic reducing agent L-Selectride R so as to avoid possible decomposition of the aldehyde 70 that was initially generated. Oxazoline 71 was thus obtained in 86% yield and could be transformed in two further steps either to 2 or the glycosyl acceptor 21 employed in Danishefsky's synthesis of 1.…”

Synthesis of a New Allosamidin Analog,N,N′-Diacetyl-β-Chitobiosyl Allosamizoline, and Its Inhibitory Activity against Some Chitinases

“…We have recently achieved a total synthesis of 1,7) which involved the efficient conversion of N,N'-diacetylchitobiose into the corresponding diastereomeric disaccharide with a pair of allo configurations, and its coupling with an allosamizoline derivative. Direct glycosidation between the N,N'.…”

“…Our synthesis is based on a convergent process, including a glycosidation reaction with glycosyl donor 5 and glycosyl acceptor 6. One segment (5) was synthesized from thioglycoside 3,7) which was prepared through an enzymatic degradation of chitin 8 ) followed by synthetic modifications. All the acetyl groups of 3 were removed by successive treatments with a base.…”

“…The good results of this glycosidation reaction are in sharp contrast to those of a similar coupling between the 3,3'-epimer of 5 and 6 during the previous total synthesis of 1, which gavethe glycal type of side product in about a 48% yield. 7 ) It is interesting that the configuration at the C-3 position of the glycosyl donor crucially affected such glycosidation reactions. Finally, simultaneous deprotection of the O-acetyl group and Nphthaloyl group of 7 was performed with methylamine in ethanol,lO) and subsequent N-acetylation of the resulting compound and then debenzylation in the presence of 10 % Pd/C under a hydrogen atmosphere yielded allosamidin analog 2.…”