1412914-93-2

Upstream product

• 868598-89-4 3-{3-chloro-4-(benzyloxy)phenyl}acrylic acid ethyl ester 
• 1412914-90-9 ethyl (2R,3S)-2,3-dihydroxy-3-(4-benzyloxy-3-chlorophenyl)propionate 
• 100836-85-9 (R)-2-benzyloxypropionic acid 
• 115458-99-6 methyl (2R)-2-(benzyloxy)propanoate 
• 81927-55-1 O-benzyl 2,2,2-trichloroacetimidate 

Relevant academic research and scientific papers

A general and scalable synthesis of aeruginosin marine natural products based on two strategic C(sp3)-H activation reactions

An efficient and scalable access to the aeruginosin family of marine natural products, which exhibit potent inhibitory activity against serine proteases, is reported. This synthesis was enabled by the strategic use of two different, recently implemented C(sp3)-H activation reactions. The first method led to the common 2-carboxy-6-hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second one provided rapid and divergent access to the various hydroxyphenyllactic (Hpla) subunits. This strategy allowed the synthesis of the aeruginosins 98B and 298A, with the latter being obtained in unprecedentedly large quantities.

Divergent Synthesis of Aeruginosins Based on a C(sp3)￡H Activation Strategy

A general and scalable access to the aeruginosin family of marine natural products, exhibiting potent inhibitory activity against serine proteases, is reported. This was enabled by the strategic use of two recently implemented Pd-catalyzed C(sp3)￡H activation reactions. The first method allowed us to obtain the common 2-carboxy-6-hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second method provided a rapid and divergent access to various hydroxyphenyllactic (Hpla) subunits, including halogenated ones. This unique strategy, together with an optimization of the fragment coupling sequence allowed the synthesis of four aeruginosins, that is, 98A-C and 298A from the chiral pool. Among them, aeruginosin 298A was synthesized on an unprecedentedly large scale. In addition, halogenated aeruginosins 98A and 98C were synthesized for the first time, thanks to a fine-tuning of the final hydrogenation step. Go natural! A general and scalable access to the aeruginosin family of marine natural products (see graphic), exhibiting potent inhibitory activity against serine proteases, is described. The strategic use of two different Pd-catalyzed C(sp3)￡H activation reactions led to the synthesis of aeruginosins98A-C and 298A.

Total synthesis of aeruginosin 98B

The first total synthesis of aeruginosin 98B was accomplished. The key step is a highly diastereoselective Pd-catalyzed intramolecular asymmetric allylic alkylation reaction of a diastereomeric mixture of allylic carbonates that is enabled by the use of racemic phosphine ligand L1.