134639-65-9Relevant academic research and scientific papers
Carbohydrate-based synthetic approach to control toxicity profiles of folate-drug conjugates
Vlahov, Iontcho R.,Santhapuram, Hari Krishna R.,You, Fei,Wang, Yu,Kleindl, Paul J.,Hahn, Spencer J.,Vaughn, Jeremy F.,Reno, Daniel S.,Leamon, Christopher P.
, p. 3685 - 3691 (2010)
Figure presented To better regulate the biodistribution of the vinblastine-folate conjugate, EC145, a new folate-spacer that incorporates 1-amino-1-deoxy-d-glucitol-γ-glutamate subunits into a peptidic backbone, was synthesized. Synthesis of Fmoc-3,4;5,6-di-O-isopropylidene-1-amino-1-deoxy- d-glucitol-γ-glutamate 20, suitable for Fmoc-strategy solid-phase peptide synthesis (SPPS), was achieved in four steps from δ-gluconolactone. Addition of alternating glutamic acid and 20 moieties onto a cysteine-loaded resin, followed by the addition of folate, deprotection, and cleavage, resulted in the isolation of the new folate-spacer: Pte-γGlu-(Glu(1-amino-1-deoxy- d-glucitol)-Glu)2-Glu(1-amino-1-deoxy-d-glucitol)-Cys-OH (21). The addition of 21 to an appropriately modified desacetylvinblastine hydrazide (DAVLBH) resulted in a conjugate (25) with an improved therapeutic index. Treatment of 25 with DTT in neutral buffer at room temperature demonstrated that free DAVLBH would be released under the reductive environment of the internalized endosome.
A convenient synthesis of hexulosonic acids by IBX mediated oxidation of D-glucono-1,5-lactone derivatives
Kolender, Adriana A.,Puenzo, Sol C. Parajon,Varela, Oscar
scheme or table, p. 237 - 244 (2011/06/10)
The oxidation of the free hydroxyl group of methyl 3,4:5,6-di-O- isopropylidene-D-gluconate 2 or its 2,3:5,6-di-O-isopropylidene analogue 3, the products of acetonation of D-glucono-1,5-lactone 1, has been attempted by alternative procedures. The oxidation of OH-2 in 2, or OH-4 in 3, with o-iodoxybenzoic acid (IBX) took place to afford the respective 2-keto 4 and 4-keto 7 derivatives in almost quantitative yields. In contrast, the oxidations with pyridinium dichromate were unsuccessful, and those using dimethylsulfoxide?acetic anhydride afforded low yields of 4 or 7. Selective removal of the isopropylidene groups in 4 or 7 with 88% aqueous acetic acid afforded, respectively, the methyl esters 5 or 8; whereas treatment with aqueous trifluoroacetic acid led to the free hexulosonic acids 6 or 9. The tautomeric preferences for the oxidation products 4 and 7, and their derivatives, have been established by 13C NMR spectroscopy. ARKAT-USA, Inc.
A two-step preparation of a new C4 chiral building block derivative of D-erythronic acid
De Souza,Da Silva,Ferreira
, p. 1339 - 1340 (2007/10/03)
1,2;3,4-Di-O-isopropylidene-D-erythronic acid (2,2,2′,2′-Tetramethyl-[R,R-(4,4′-bi-1,3-dioxolan)]-5-one) 4, a new C4 chiral building block derivative of D-erythronic acid was prepared in two steps from D-glucono-δ-lactone.
