Aeruginosins

Aeruginosine A (254) (69JCS(C)2514) and B (255) (61MI2), shown in Scheme 83, are metabolites of the pyocyanine producing Pseudomonas aeruginosa. They are isoconjugate with the odd alternant 1-isopropenyl-anthracene anion (class 13). 

Cyanobacteria -Microcystis aeruginosa Aeruginosins 298-A and -B -thrombin and trypsin inhibitors 266-269... 

Cyanobacteria -Microcystis Aeruginosin EI461 - protease inhibitor 266, 270, 271... 

HO3SO H Cyanobacteria -Microcystis aeruginosa Aeruginosins 98-A, 98-B, 98-C, and 101 - trypsin inhibitors 266, 269, 273... 

COjH H Cyanobacteria -Osciiiatoria agardhii Aeruginosins 205A and 205B -trypsin and thrombin inhibitors 266, 274... 

The marine natural product dynosin A 144 is a member of the aeruginosin family and an inhibitor of thrombin and Factor Vila. In Hanessian s total synthesis of 144,both the dihydroxy-octahydroindole 137 and the pyrroline moiety 138 have been prepared by RCM-based routes (Scheme 25). 

Murakami M, Ishida K, Okino T, Okita Y, Matsuda H, Yamaguchi K (1995) Aeruginosins 98-A and B, Trypsin Inhibitors from the Blue-Green Alga Microcystis aeruginosa (NIES-98). Tetrahedron Lett 36 2785... 

Shin HJ, Matsuda H, Murakami M, Yamaguchi K (1997) Aeruginosins 205A and -B, Serine Protease Inhibitory Glycopeptides from the Cyanobacterium Oscillatoria agardhii (NIES-205). J Org Chem 62 1810... 

Ishida K, Okita Y, Matsuda H, Okino T, Murakami M (1999) Aeruginosins, Protease Inhibitors from the Cyanobacterium Microcystis aeruginosa. Tetrahedron 55 10971... 

Vails N, Lopez-Canet M, Vallribera M, Bonjoch J (2000) Total Synthesis and Reassignment of Configuration of Aeruginosin 298-A. J Am Chem Soc 122 11248... 

Very recently the Shibasaki group extended the range of application of their asymmetric two-center catalysts 31 to the synthesis of amino acid derivative intermediates for aeruginosin 298-A and analogs thereof [39]. Aeruginosin has a tetrapeptide-like structure and contains non-standard a-amino acids. The synthesis of the key intermediate (S)-20r, bearing a bulky substituent, is shown in Scheme 3.17 [39]. In the presence of the catalyst R,R) 31 the desired amino acid derivative (S)-20r was obtained in 80% yield and with 88% ee [39]. The catalyst 31, which is very stable under basic conditions, could be recovered in 80-90% yield and re-used efficiently [39]. 

The aeruginosins are a class of cyanobacterial peptide incorporating two characteristic structural features an N-terminal hydroxyphenyllactic acid residue and the highly unusual amino acid 2-carboxy-6-hydroxy-octahydroindole (Choi). The structural diversity, synthesis, and biological activity of this structure class have recently been reviewed. The first example was aeruginosin 298-A (40), isolated from M. aeruginosa NIES-298. ° The structure was elucidated primarily by 2D NMR however, the absence of any NMR... 

The aeruginosins and their derivatives are of hiological interest due to their activity as inhibitors of serine proteases, in particular those involved in hlood coagulation. Metabolite 40 has been cocrystallized with thrombin while aeruginosin 98-B (43) has been crystallized with trypsin, shedding some light on their... 

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