Early diagnosis and treatment of Alzheimer's disease by targeting toxic soluble Aβ oligomers.

Transient soluble oligomers of amyloid-β (Aβ) are toxic and accumulate early prior to insoluble plaque formation and cognitive impairment in Alzheimer's disease (AD). Synthetic cyclic D,L-α-peptides (e.g.

Synthesis of 5- and 7-hydroxy indolizidin-2-one prostaglandin-F modulators and activity on myometrial contractility towards development of agents for delaying preterm birth.

In pursuit of more effective-labor delaying tocolytic agents, the prostaglandin F2α (PGF2α) receptor (FP) modulator PDC113.824 [(6S)-2] represents a potent lead for developing therapy to treat preterm birth. Derivatives of FP modulator (6S)-2 were synthesized, possessing respectively 5- and 7-hydroxyl groups on the indolizidin-2-one amino acid (I aa) residue.

Constrained Dipeptide Surrogates: 5- and 7-Hydroxy Indolizidin-2-one Amino Acid Synthesis from Iodolactonization of Dehydro-2,8-diamino Azelates.

The constrained dipeptide surrogates 5- and 7-hydroxy indolizidin-2-one -(Boc)amino acids have been synthesized from L-serine as a chiral educt. A linear precursor ∆-unsaturated (2,8)-2,8-bis[-(Boc)amino]azelic acid was prepared in five steps from L-serine. Although epoxidation and dihydroxylation pathways gave mixtures of hydroxy indolizidin-2-one diastereomers, iodolactonization of the ∆-azelate stereoselectively delivered a lactone iodide from which separable (5)- and (7)-hydroxy indolizidin-2-one -(Boc)amino esters were synthesized by sequences featuring intramolecular iodide displacement and lactam formation.

6-Hydroxymethyl Indolizidin-2-one Amino Acid Synthesis, Conformational Analysis, and Biomedical Application as Dipeptide Surrogates in Prostaglandin-F Modulators.

6-Hydroxymethyl indolizidin-2-one amino acids were synthesized in 10 steps from l-serine by intramolecular ring opening of a symmetrical epoxide and lactam formation. X-ray analyses indicated the bicycles replicated ideal peptide type II' β-turn central dihedral angle geometry. Inside a prostaglandin-F receptor modulator, the 6-hydroxymethyl analogue retained inhibitory activity on myometrial contractility.

4-Vinylproline.

Enantiomerically pure 4-vinylproline (Vyp) was synthesized by a five-step approach from N-(Boc)iodo-alanine (2) featuring copper-catalyzed S2' substitution of the corresponding zincate onto ( Z)-1,4-dichlorobut-2-ene to prepare methyl 2- N-(Boc)amino-4-(chloromethyl)hexenoate (3). Intra- and intermolecular displacement of the chloride provided respectively Vyp and methyl 2- N-(Boc)amino-4-(azidomethyl)hexenoate (7) suitable for the synthesis of constrained peptide analogs.