(–)‐Blebbistatin (1), a recently discovered small molecule inhibitor of the ATPase activity of non‐muscle myosin II has been prepared from methyl 5‐methylanthranilate (6) in three steps. This flexible synthetic route has also been used to prepare a nitro group‐containing analogue 12 that has modified fluorescence properties and improved stability under microscope illumination. The key step in the synthesis of 1 and its analogues was the asymmetric hydroxylation of the quinolone intermediate 3 using the Davis oxaziridine methodology. The absolute stereochemistry of (–)‐blebbistatin (1) was shown to be S by X‐ray crystal structure analysis of a heavy atom (bromine) containing analogue 11, which was subsequently reduced and shown to be identical to 1. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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SummaryThe precursor synthesis and the no-carrier-added (n.c.a.) radiosynthesis of the adenosine-A 1 receptor ligand 5Se]1) are described in this report. A method was developed starting from elemental n.c.a. selenium-75, followed by a three-step polymer-supported radioselenation and deprotection which gave the radioligand with a radiochemical yield of 30%, a radiochemical purity of >99% and a specific radioactivity of >300 GBq/mmol (8 Ci/ mmol). Preparation time was 40 min. The nonradioactive compound 5 0 -(methylseleno)-N 6 -cyclopentyladenosine (1) was pharmacologically evaluated in vitro and showed high affinity and selectivity for the adenosine-A 1 receptor. These preliminary results suggest that this compound could be a useful radioligand for the noninvasive imaging of the brain adenosine-A 1 receptors using positron emission tomography (PET) when labelled with the positron emitter selenium-73 (half-life: 7.1 h).

The present work describes two radiosynthetic pathways to prepare homocysteine[ 75 Se]selenolactone 1 starting from n.c.a. [ 75 Se]selenite 2. It was achieved either by alkylation reaction of n.c.a. methyl[ 75 Se]selenide 4 or by hydrolysis of alkylated 1,3-dicyclohexyl[ 75 Se]selenourea 11. N.c.a. methyl[ 75 Se]selenide 4 is available using sulfur as non-isotopic carrier. However, the radiochemical yield of the substitution of 2-tert.-butoxycarbonylamino-4-bromobutyric acid ethylester 5 with n.c.a. methyl-[ 75 Se]selenide is only in the range of 15%-20%. Birch reduction of protected n.c.a. [ 75 Se]selenomethionine 6 formed leads to a RCY of 5%-10% homocysteine[ 75 Se]selenolactone 1. Alternatively, the synthesis of homocysteine[ 75 Se]selenolactone 1 is possible by hydrolysis of the corresponding [ 75 Se]selenouronium salt 11 available by addition of 2-tert.-butoxycarbonylamino-4-bromobutyric acid ethylester 5 to 1,3-dicyclohexyl[ 75 Se]selenourea 10. A method was developed for the synthesis of 1,3-dicyclohexyl[ 75 Se]selenourea 10 by addition of c.a. [ 75 Se]SeH 2 to 1,3-dicyclohexylcarbodiimide, which leads to 20%-30% RCY of c.a. homocysteine[ 75 Se]selenolactone 1.

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