A chemoenzymatic approach to (+)-pilocarpine

Concise Synthesis of Both Enantiomers of Pilocarpine

“…In our own synthetic strategy, the introduction of the 1-methylimidazole residue should be the last step of the synthesis, since this residue—as previously shown [ 42 ] —can be introduced in a single step and under very mild conditions using a Leusen imidazole synthesis [ 58 , 59 , 60 , 61 ]. However, a prerequisite for carrying out this planned synthetic sequence is that (homo)-pilopaldehyde or (homo)-pilopic acid must be present in pure enantiomeric and diastereomeric forms.…”

“…However, the content of (+)-1 is very low in the leaves of different species of trees of the genus Pilocarpus ; it ranges from 0.12–0.6% in P. racemosous [ 30 , 31 , 32 ] and from 0.45% in P. microphyllus [ 33 , 34 , 35 ] and P. pennatifolius [ 36 , 37 ] to 0.8% in P. jaborandi [ 38 , 39 ]. Due to the low content of the alkaloid in the plant material as well as a laborious extraction procedure [ 40 ], a number of syntheses have been described for this interesting molecule [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. Many of them, however, are multi-step and laborious, often of low yield, or they yield a racemic product.…”

“…In the context of our own studies on inhibitors of carbonic anhydrases, we were interested in an efficient access to (+)-1 but also its enantiomer (–)-1 . This approach uses, in part, a chemoenzymatic strategy that we have previously [ 42 ] used to synthesize natural occurring (+)-1 .…”

Imidazole derivatives for efficient organic light-emitting diodes

“…Imidazole is stable at 400°C, possesses a considerable aromatic character, and undergoes the usual electrophilic aromatic substitution reactions, which are stable for OLED fabrication [14]. Several imidazole synthesis methods are reported in literatures, such as molecular rearrangement [15], ring opening [16], cyclization [17], parallel synthesis [18], direct oxidative conversion [19], solid-phase synthesis [20], one-pot synthesis [21], twopot synthesis [22], flash vacuum pyrrolysis [23], microreactor [24], ionic-liquid-promoted synthesis technique [25], and the catalytic [26] and chemoenzymatic methods [27,28]. Multicomponent reactions through the cyclocondensation of aromatic aldehyde, ammonium acetate, aniline, and benzyl have been proven to be successful in generating multi-substituted imidazoles in a single synthetic operation (Scheme 1).…”

The role of the GGGX motif in determining the activity and enantioselectivity of pig liver esterase towards tertiary alcohols

“…Lately, the effi cient synthesis of oseltamivir phosphate (Tamifl u ™ ) was reported by Zutter et al (2008) including an enzymatic desymmetrization step with PLE. Other recent enantioselective hydrolyses catalyzed by PLE were published by Asakawa et al (2008) and Csuk & Woeste (2008). The state-of-the-art use of PLE as a biocatalyst in organic synthesis has been also reviewed (Dom í nguez de Mar í a et al 2007).…”