Mikrobiologische und Enzymatische Reaktionsstufen in der Synthese von Prostacyclin‐Analoga

Abstract

Microbiological and Enzymatic Transformations in the Synthesis of Prostacyclin Analogues For the synthesis of prostacyclin analogues, enzymatic and microbiological transformations are described leading to homochiral bicyclooctane building units.

Bicyclic β-amino acids

“…When an analogous reaction sequence was applied to (+)-2-carene (23), the first step was not regioselective, so that 1 : 1.6 to 1 : 2.1 mixture of the corresponding lactams 24 and 25 was obtained. 20 Owing to this, both amino acids 6 and 7 were obtained after multistep hydrolysis of 24 and 25.…”

“…Derivatives of amino acid 8 (abbreviated by authors as Bic(OH)) were obtained from optically active precursor 26 (Scheme 4), 22 which in turn was obtained by chemoenzymatic resolution of readily available bicyclo[3.3.0]octane derivatives. 23 The free amino acid 8 was not isolated; for the incorporation of its residue in peptides by solidphase synthesis, ketal 27 was used. After applying standard Fmoc protocol, peptides containing the residue of 27 were cleaved from the resin with TFA -Et 3 SiH; upon these conditions, ketal deprotection as well as stereoselective reduction occurred.…”

Stereocontrolled synthesis of all eight stereoisomers of the putative anti-androgen cyoctol

“…Both enantiomers of 22 were thus available in multigram quantities. 15 Swern oxidation of 22 led to the keto-enol ester 23 which was subjected to a Trost-Tsuji allylation 16 with acetates 18 and 21, respectively. Acetate 18 was prepared from alcohol 16 as shown in Scheme 3; Mitsunobu inversion 17 of alcohol 15 gave 19 which was transformed into allyl acetate 21 as shown.…”

Development of Chiral Building Blocks Having a Bicyclo[3.3.0]Octane Framework Using a Diastereomeric Resolution‐Selective Deprotection

“…Enantiomerically pure compounds could become important chiral building blocks in the production of fine chemicals with applications as pharmaceuticals, or of valuable chiral auxiliaries with applications as ligands of enantiomerically pure reagents or catalysts in organic synthesis. [1][2][3][4][5][6][7][8][9] Specifically, enantiomerically pure bicyclo [3.3.0]octane derivatives could become useful chiral building blocks because the bicyclo [3.3.0]octane framework is a common structural building block of a variety of natural products and pharmaceutical compounds that contain substituted pentalenes such as some carbacyclins, [10][11][12] sesquiterpenoids, 11,[13][14][15][16][17][18] macrolactams, 18,19 and so on 18,20 (Fig. 1) 13,21 .…”