Disaccharide blocks for analogs of OSW-1

Abstract

The acetalization of phenyl 1-thio-α-L-arabinopyranoside with 2,3-butanedione in the medium of MeOH-CH(OMe) 3 -CSA proceeded with the prevailing formation of the corresponding 3,4-bisacetal that further was converted in compounds, which were regio-and stereoisomers of disaccharide block of OSW-1. O HO O SPh HO OH HO O SPh HO OAc I II IIIIn the sugar chemistry the necessity to work with awkward polyol systems makes the protective groups extremely important [1]. In the course of the planned synthesis of disaccharide block I for anticancer steroid OSW-1 based on the known components, glycosidedonor II and acceptor III [2, 3] (Scheme 1) we tested 2,3-butanedione in conditions described in [4] for the selective protection of the 3,4-diol moiety of triol II in the form of butane 2,3-bisacetal. The butane 2,3-bisacetal and the other similar protective groups introduced into the synthetic practice by Liu group [5] are known to provide a selective blocking in cycles of trans-vicinal diols, impart the products a crystalline structure, desired conformational rigidity, etc. [6].As seen from the structure of triol II all its hydroxy groups are located in the trans-equatorial reciprocal position, and here the possibility of the regiocontrolled acetalization depends mainly on the steric factors. In the experimental test of triol II acetalization by heating with excess 2,3-butanedione in the medium of MeOH-CH(OMe) 3 -camphorsulfonic acid (CSA) (catalyst) we obtained two expected acetals IV and V in the ratio ~3 : 1 and in the overall yield 80%. The main bisacetal IV is a crystalline substance easily isolated from compound V by chromatography on SiO 2 . Minor bisacetal V is oily substance containing ~10% of unidentifi ed isomeric compound. The assignment of the structure of regioisomeric acetals IV and V was carried out applying spectral data. Their 1 H NMR spectra contain a characteristic signal C 1 H which in the spectrum of 2,3-acetal V is located downfi eld (doublet, δ 4.77 ppm, J 9.6 Hz) with respect to the corresponding signal in the spectrum of compound IV (δ 4.47 ppm, d, J 9.35 Hz) because of the electron-withdrawing inductive effect of the closely Scheme 1.

Synthesis and Antiproliferative Activities of OSW‐1 Analogues Bearing 2”‐O‐p‐Acylaminobenzoyl Residues†

“…The resulting thioxyloside was treated with NaOCH 3 in a mixture solvent of CH 3 OH and CH 2 Cl 2 at rt to remove the acetyl groups; [ 48 ] subsequent protection under the conditions of 2,3‐butanedione and CH(OMe) 3 in the presence of BF 3 ·OEt 2 provided 5 in an overall yield of 35% (based on 4 ). [ 49‐51 ] As a precursor of the desired p ‐aminobenzoyl group for late‐stage acylation, the relatively inert p ‐nitrobenzoyl (PNB) group was introduced into alcohol 5 to give 6 in 91% yield under the conditions of PNBCl, DIPEA, and DMAP in CH 2 Cl 2 . Treatment of thioglycoside 6 with NBS and H 2 O resulted in hemiacetal 7 in 98% yield, which was a ready precursor for further preparation of imidate and ortho‐ alkynylbenzoate donors.…”

Synthese von Aeruginosin‐Chlorsulfopeptiden und Untersuchung ihrer Toxizität

“…Die selektive Anbringung der Sulfat-Gruppe an der O4-Position des Xylosyl-Substituenten erforderte eine orthogonale Schutzgruppenstrategie hinsichtlich der Positionen O2 und O3, sodass wir für O4 eine basenlabile und für O2 und O3 eine säurelabile Schutzgruppe wählten. [10] Vorausgegangene Versuche zur Anbringung der BDA-Schutzgruppe hatten stets zu einer Mischung verschiedener Isomere geführt;e rst durch Optimierung der Reaktionsbedingungen konnte das Xylose-Derivat 6 diastereomerenrein erhalten werden. [8] An der Position O4 konnte durch Reaktion mit Benzoylchlorid und Me 2 SnCl 2 als Katalysator regioselektiv eine Benzoyl(Bz)-Schutzgruppe angebracht werden (81 %A usbeute).…”

“…[9] Die Hydroxygruppen an Position 2und 3 wurden durch Reaktion mit 2,3-Butandion und Tr imethylorthoformiat in Gegenwart von Camphersulfonsäure als Butandiacetal (BDA) geschützt. [10] Vorausgegangene Versuche zur Anbringung der BDA-Schutzgruppe hatten stets zu einer Mischung verschiedener Isomere geführt;e rst durch Optimierung der Reaktionsbedingungen konnte das Xylose-Derivat 6 diastereomerenrein erhalten werden. Der 1-(N-Amidino-D 3 -pyrrolino)ethyl(Adc)-Seitenkettenbaustein 8 wurde durch Modifikation einer Vorschrift von Hanessian et al erhalten, [11] die ausgehend von kommerziell erhältlichem a-Methylen-g-butyrolacton in zehn Stufen mit 8% Gesamtausbeute zum Dihydropyrrol-Intermediat 7 führt.…”

Chemistry of xylopyranosides

“…293 Later on, selectivity for the 3,4-BDA product was achieved using both 2,2,3,3-tetramethoxybutane and butane-2,3-dione (Scheme 16). 86,252,[294][295] Scheme 16. Reagents and conditions: (a) 2,2,3,3-Tetramethoxybutane, BF3⋅Et2O, MeCN.…”