154456-39-0

Upstream product

• 163493-02-5 (R)-2-(N,N-dibenzylamino)-3-O-benzyl-1,3-propanediol 
• 4726-96-9 O-Benzyl-L-serine 
• 100-39-0 benzyl bromide 

Downstream Products

• 847983-97-5 (3R,4S)-5-Benzyloxy-4-dibenzylamino-1-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pent-1-yn-3-ol 
• 847984-01-4 [(1S,2R)-1-Benzyloxymethyl-4-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-2-hydroxy-butyl]-carbamic acid tert-butyl ester 
• 847984-05-8 ((1S,2R,5S)-1-Benzyloxymethyl-2,5,6-trihydroxy-hexyl)-carbamic acid tert-butyl ester 
• 847984-09-2 [(S)-2-Benzyloxy-1-((2R,5R)-5-hydroxymethyl-tetrahydro-furan-2-yl)-ethyl]-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Total synthesis and stereochemistry revision of mannopeptimycin aglycone

Development of efficient methods for preparation of bioactive nonribosomal peptides, containing densely functionalized nonproteinogenic amino acids, is an important task in organic synthesis. We have employed a concise synthesis for such amino acids by asymmetric aldol addition coupled with an isomeric resolution via diastereoselective cyclization. This approach is successfully applied to the first total synthesis of the cyclic hexapeptide aglycone of the mannopeptimycins, a group of glycopeptides known for potent activity against drug-resistant bacteria. The facile preparation of the key amino acids and the synthesis of the aglycone pave the way for further studies on this class of antibiotics and the development of new lead compounds with therapeutic potential. In addition, our studies have led to the revision of the stereochemistry of the β-methylphenylalanine residue in the mannopeptimycin aglycone.

Generation of Leads for γ-Secretase Modulation

Herein, we disclose three structurally differentiated γ-secretase modulators (GSMs) based on an oxadiazine scaffold. The analogues from series I potently inhibit the generation of Aβ42 in vitro when the substituents at 3 and 4 positions of the oxadiazine moiety adopt an α orientation (cf. 11). To address the concern around potential reactivity of the exocyclic double bond present in series I toward nucleophilic attack, compounds containing either an endocyclic double bond, such as 20 (series II), or devoid of an olefinic moiety, such as 27 (series III), were designed and validated as novel GSMs. Compound 11 and azepine 20 exhibit robust lowering of CSF Aβ42 in rats treated with a 30 mg/kg oral dose.