Synthesis and Conformational Analysis of Macrocyclic Dilactones Mimicking the Pharmacophore of Aplysiatoxin

Abstract

A small number of macrocyclic dilactones of type 3, i.e., 9, 10, 11, and epi-11, comprising a 3,4-dihydroxypentanoic acid unit, the pharmacophore of aplysiatoxin, and a conformationally preorganized whydroxynonanoic acid unit were synthesized. Conformational analysis ± based on 2 J and 3 J NMR coupling constants ± of the dihydroxypentanoyl part of these macro-dilactones indicates the extent to which a conformation induction across the macro-dilactone ring occurs from the stereogenic centres implemented in the w-hydroxynonanoic acid part.

Synthesis of the Aglycon of the Antibiotic Disciformycin

“…The synthesis towards the linear precursor started from methyl ( R )‐lactate ( 6 ) (Scheme ). This was converted into alkene 15 after O ‐protection, reduction to the aldehyde followed by a chelation controlled Hosomi–Sakurai allylation,, and O ‐silylation. Next, ozonolysis provided the aldehyde which was subjected to Wittig olefination conditions to yield ethyl ester 16 with excellent stereocontrol (> 10:1).…”

Stereoselective Synthesis of the Monomeric Unit of SCH 351448

“…Both building blocks 4 and 5 share a cis-2,6-disubstituted tetrahydropyran (THP) ring as the common motif. Starting point for the synthesis of the phosphonium salt 3 was N,N-dimethyl-3-methoxy benzylamine (6) configuration of 14 was assigned by NMR based on a H2-H6 NOE contact. Ozonolysis of the terminal double bond in 14 gave the aldehyde 4.…”

“…MTBE = tert-butyl methyl ether. 2,2-Ethylendioxy-5-hexene (9): [6] To a solution of acetoacetic acid ester 8 (117 mL, 0.92 mol) in ethanol (300 mL) sodium (17.3 g, 0.76 mol) was added and the resulting solution was cooled to 0°C. Allylbromide (59 mL, 0.69 mol) was added over 30 min and the solution was stirred for 3 h at 20°C and 4 h at 60°C.…”

Synthesis and Refunctionalization of Hexahydro-naphthalenone Systems

“…A solution of rac-BINOL (616 mg, 2.15 mmol) in CH 2 Cl 2 (15 mL) was added to a suspension of molecular sieves (4 Å, 5g) in CH 2 …”