Total Synthesis of Cryptoconcatone D via Construction of 1,3-Diol Units Using Chiral Horner–Wittig Reagents

Abstract

The modular synthesis of 1,3-polyols using a chiral phosphine oxide building block is reported. This versatile building block works in a repetitive way for the stereocontrolled synthesis of a tetraol key intermediate, which serves for the first total synthesis of the potentially anti-inflammatory natural product cryptoconcatone D. A new route toward the chiral building block is also presented: Starting from 2-deoxy-d-ribose, the optimized sequence now makes the use of the building block more attractive to practicing chemists again.

Synthesis of the monomeric counterpart of Marinomycin A and B

“…12 The polyol fragments 7 and 8 should be linked together using Julia-Kocienski olefination. [13][14][15] The introduction of the densely substituted aromatic core was planned through a photochemical esterification method following the protocol established by de Brabander et al [16][17][18] 1,3-Polyols were introduced on the basis of our previously described strategies. 19,20 we planned to employ the chiral building blocks 10 and 11 in an iterative fashion for the construction of the polyol-containing fragments 7 and 8.…”

“…12 The polyol fragments 7 and 8 should be linked together using Julia–Kocienski olefination. 13–15 The introduction of the densely substituted aromatic core was planned through a photochemical esterification method following the protocol established by de Brabander et al 16–18…”

Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin Analogues

“…These two compounds have been completely neglected thus far and rarely studied. There are described chemical procedures for the synthesis of cryptoconcatones D, H and I [ 45 , 46 , 47 ]. However, there are no pharmacological studies defining their molecular target and activities.…”

Total synthesis of both enantiomers of the biosurfactant aureosurfactin via bidirectional synthesis with a chiral Horner–Wittig building block

“…For the synthesis of both enantiomers 2a and 2b we selected our recently developed modular strategy for the diastereoselective synthesis of syn - and anti -1,3-polyol units based on the chiral diphenylphosphane oxide (6 S )- 3 (Scheme 1), 19,20 which can be easily prepared from readily available and inexpensive 2-deoxy- d -ribose in seven steps. 21 A Horner–Wittig reaction with aldehydes 4a (R = n Pr) and 4b (R = OPMB), respectively, and a subsequent syn -reduction should provide the 1,3-diols 5a and 5b . The preparation of (3 S ,5 S )-3,5-dihydroxydecaonic acid derivative 2a should be obtained from 5a via sequential silyl protection.…”