Asymmetrized 2-Methyl-1,3-propanediol and Its Equivalents: Preparation and Synthetic Applications

Total synthesis of (+)-phorboxazole A, a potent cytostatic agent from the sponge Phorbas sp.

“…26 Our own synthesis, which is summarised in Scheme 4, started with the chiral pool ester 37, and proceeded via the protected 1,3,5-triol 42 and the epoxide 48 as key intermediates. 11 Thus, following the conversion of methyl (S )-3hydroxy-2-methylpropionate 37 27 into the known aldehyde 38, 28 a crotylboration reaction using (Ϫ)-methoxydiisopinocampheyborane and E-2-butene 29 next led to the substituted secondary alcohol 39 with 98% diastereoselectivity and in 76% yield. The protecting groups in 39 were then interchanged and the resulting alkene 40b was cleaved oxidatively producing the corresponding aldehyde 41.…”

“…With the three sub-units 3, 4 and 5 in phorboxazole A now synthesised, we examined their assembly to the natural product focusing on the stereocontrolled formation of the alkene bonds at C(2-3), C(19-20) and C (27)(28). Our first strategy was to link the units 4 and 5 at C(19-20), and then to elaborate the macrolide 89 using an intramolecular Wadsworth-Emmons reaction at C(2-3) which had been highlighted in the first synthesis of phorboxazole A by Forsyth et al 4 We then planned to complete the synthesis of 1a by linking 89 to 3 (R᎐ ᎐ SO 2 Ar) using a stereoselective Julia reaction.…”

“…Following the disappointing outcome of our attempts to directly link the macrolide portion 89 to the side chain residue 36 in phorboxazole, we decided to follow a new strategy to the natural product. This strategy was based on first attaching the oxane methyl ketone 4 to the side chain oxazole at C (27)(28) leading to the oxane-oxazole 90. Encouraged by precedent established by Evans et al 5b and others, 47 we next planned to couple the side chain lactone 91 to the methyloxazole 90 using metallation chemistry, leading to the cyclic hemiacetal 92.…”

Enzyme in organischen Lösungsmitteln: Eigenschaften und Einsatz in der Synthese

“…[114] So wurde die durch Schweinepankreas-Lipase katalysierte Desymmetrisierung des Diols 37 im 40-g-Maûstab durchgeführt. [114] So wurde die durch Schweinepankreas-Lipase katalysierte Desymmetrisierung des Diols 37 im 40-g-Maûstab durchgeführt.…”

Asymmetrized Tris(hydroxymethyl)methane and Related Synthons: Enantioselective Preparation and Synthetic Applications

“…[10] Thus the allylated compound 60, after conversion into the isopropylidene derivative 61, was hydroborated and oxidized to the aldehyde 62. It was then coupled with enantiomerically pure sulfone 63 (prepared from a different Scheme 14 building block, namely 3-hydroxy-2-methyl propanoate) [27] to give 64 which is a key intermediate for the synthesis of hypocholesterolemic agent 1233A.…”