RESUMEN
Heparan sulfate (HS) has multifaceted biological activities. To date, no libraries of HS oligosaccharides bearing systematically varied sulfation structures are available owing to the challenges in synthesizing a large number of HS oligosaccharides. To overcome the obstacles and expedite the synthesis, a divergent approach was designed, where 64 HS tetrasaccharides covering all possible structures of 2-O-, 6-O- and N-sulfation with the glucosamine-glucuronic acid-glucosamine-iduronic acid backbone were successfully produced from a single strategically protected tetrasaccharide intermediate. This extensive library helped identify the structural requirements for HS sequences to have strong fibroblast growth factor-2 binding but a weak affinity for platelet factor-4. Such a strategy to separate out these two interactions could lead to new HS-based potential therapeutics without the dangerous adverse effect of heparin-induced thrombocytopenia.
Asunto(s)
Heparitina Sulfato , Oligosacáridos , Oligosacáridos/química , Heparitina Sulfato/química , Unión Proteica , Ácido Glucurónico/metabolismo , GlucosaminaRESUMEN
Stereoselective synthesis of S-linked trisaccharide glycal of angucycline antitumor antibiotic derhodinosylurdamycin A is described. The synthesis has been accomplished employing our previously reported umpolung S-glycosylation strategy - stereoselective sulfenylation of 2-deoxy glycosyl lithium. It was found that sugar-derived thiocyanate was a better electrophile than corresponding asymmetric disulfide in this type of stereoselective sulfenylation.
Asunto(s)
Éteres/química , Guanidinas/química , Guanidinas/síntesis química , Litio/química , Oligosacáridos/química , Oligosacáridos/síntesis química , Azufre/química , Tiocianatos/química , Trisacáridos/química , Alquilación , Técnicas de Química Sintética , Electrones , Glicosilación , EstereoisomerismoRESUMEN
Stereoselective synthesis of carbohydrate mimics resistant toward acid-mediated or enzymatic hydrolysis is chemically challenging and biologically interesting. In this Letter, the first stereoselective synthesis of a "non-hydrolyzable" S-linked hexasaccharide of antitumor antibiotic landomycin A is described. This synthesis was accomplished through the utilization of our recently developed umpolung reactivity-based S-glycosylation-sulfenylation of stereochemically defined glycosyl lithium species with asymmetric sugar-derived disulfides.
Asunto(s)
Aminoglicósidos/síntesis química , Antibióticos Antineoplásicos/síntesis química , Aminoglicósidos/química , Antibióticos Antineoplásicos/química , Glicosilación , Estructura Molecular , Estereoisomerismo , Streptomyces/química , Relación Estructura-ActividadRESUMEN
An approach for direct synthesis of biologically significant 2-deoxy-ß-glycosides has been developed via O-alkylation of a variety of 2-deoxy-sugar-derived anomeric alkoxides using challenging secondary triflates as electrophiles. It was found a free hydroxyl group at C3 of the 2-deoxy-sugar-derived lactols is required in order to achieve synthetically efficient yields. This method has also been applied to the convergent synthesis of a 2-deoxy-ß-tetrasaccharide.
Asunto(s)
Desoxiazúcares/química , Glicósidos/síntesis química , Alquilación , Estructura Molecular , EstereoisomerismoRESUMEN
A mild and atom-economic rhenium(V)-catalyzed stereoselective synthesis of ß-D-digitoxosides from 6-deoxy-D-allals has been described. This ß-selective glycosylation was achieved probably because of the formation of corresponding α-digitoxosides disfavored by 1,3-diaxial interaction. In addition, this method has been successfully applied to the synthesis of digitoxin trisaccharide glycal for the direct synthesis of digitoxin and C1'-epi-digitoxin.