A modular and organocatalytic approach to γ-butyrolactone autoregulators from Streptomycetes

Abstract

A general synthesis of optically active gamma-butyrolactone autoregulators is developed by a two-step sequence to assemble 2,3-trans-disubstituted butyrolactones in high yields and enantioselectivities; the scope of this reaction was elaborated by setting up a library of alkyl-substituted butyrolactones and the synthesis of the autoregulators IM-2 and VB-D.

In situ preparation of a multifunctional chiral hybrid organic–inorganic catalyst for asymmetric multicomponent reactions

“…Repeated runs using recycled hybrid solid as catalyst. 50 Table 2 shows that the catalytic performance of the hybrid solid remained unchanged throughout the three first runs and catalyst deactivation occurs at run 4, probably due to organocatalyst degradation and/or leaching after successive submission of the solid material to the thermal conditions used in the reaction (see 55 ESI for details).…”

“…Furthermore, combination of the homogeneous catalyst with 4 ÅMS or Silica 100 under otherwise similar conditions also furnishes the desired product in very low yield. The distinctive 50 reactivity offered by the hybrid catalyst could be attributed to the presence of the aminopropyl groups on the solid material. The primary amine sites would react with the aldehyde to form an imine intermediate, more prone to be attacked (when compared to 60 the starting aldehyde) by the deprotonated nitromethane.…”

“…Thermogravimetric analysis ( Figure S1 in the ESI) was performed in order to gain insight, not only on the organic content present in the solid, but also on the thermal stability of the organic units. Apart from the weight loss 50 observed at around 50-100ºC associated to the removal of physisorbed water, the main weight loss corresponds to the organic moieties and occurs at temperatures above 150ºC. The solid-state 13 C cross-polarization magic angle spinning (CPMAS) NMR spectrum of the solid is shown in Figure 2a C NMR for derivative 3 ( Figure 2b), corresponding to the methyls in the triethoxysilyl groups is 70 barely observed in solid 13 C CPMAS NMR of the hybrid material 4 (Figure 2a), evidencing that hydrolysis of these groups has occurred.…”

“…As a first illustration, the one reported herein bellow, as an efficient promoter of the enantioselective multicomponent reaction of aldehydes, nitromethane and malonates. The hybrid organic-inorganic material 4 was also analyzed by 50 nitrogen sorption volumetry. Table S2 in the ESI reports surface area, pore volume and mean pore diameter of the hybrid catalyst.…”

Organocatalytic Conjugate Addition in Stereoselective Synthesis

“…In 2008, Jørgensen et al reported on the Michael addition to functionalized nitroolefins for the synthesis of g-butyrolactone autoregulators, secondary metabolites of the Streptomyces species (Scheme 11.36). 70 The key stereogenic center of this family of butyrolactone was achieved via the cinchona derivative 148 catalyzed addition of suitable carbonyl donor containing an oxazolidinone such as 146. This moiety can easily be converted into the lactone by O-silyl deprotection-cyclization, affording the trans-ring junction.…”