Thromboxane B2

A stereocontrolled route to the native form of thromboxane B2 was carried out starting with a-methyl-D-glucoside (Ref. 3). 

Threonine, stereoisomers of, 302-303 structure and properties of, 1019 Threose. configuration of, 982 molecular model of, 294 Thromboxane B2. structure of,... 

A. PGArMO-TMS, PGBj-MO-TMS, PGBrMO-TMS, PGE,-MO-TMS, PGE2-MO-TMS, PGFia-TMS, 6-ketoPGFrMO-TMS, PGF2a-TMS, and thromboxane B2-TMS... 

Cyclooxygenases. Figure 1 Pathways for the formation of prostanoids from arachidonic acid. Arachidonic acid is converted by cyclooxygenase to endoperoxides, which are acted upon by various synthesases to form the prostanoids. Prostacyclin and thromboxane are relatively unstable and break down rapidly to form the inactive metabolites 6-oxo-PGF1a and thromboxane B2, respectively. 

The synthesis of thromboxane B2, the hydrolytic deactivation product of thromboxane A2, provided this material for studies of metabolism and bioactivity, and also for the development of a radioimmunassay. Two different synthetic routes were developed. 

COX = cyclooxygenase LOX = lipoxygenase POD = peroxidase PGI2 = prostacyclin, PGX TxB2 = thromboxane B2... 

Piccirillo G, Fimognari FL, Infantino V, Monteleone G, Fimognari GB, Falletti D, Marigliano V. (1994). High plasma concentrations of cortisol and thromboxane B2 in patients with depression. Am J Med Sci. 307(3) 228-32. 

Uyama O, Nagatsuka K, Nakabayashi S, Isaka Y, Yoneda S, et al. 1985. The effect of a thromboxane synthetase inhibitor, OKY-046, on urinary excretion of immunoreactive thromboxane B2 and 6-keto-prostaglandin El alpha in patients with ischemic cerebrovascular disease. Stroke 16 241-244. 

Chavali, S. R., W. W. Zhong, T. Utsunomiya, and R. A. Forse. Decreased production of interleukin-1-beta, pros-taglandin-E2 and thromboxane-B2, and elevated levels of interleukin-6 and -10 are associated with increased survival during endotoxic shock in mice consuming diets enriched with sesame seed oil supplemented with Quil-A saponin. Int Arch Allergy Immunol 1997 114(2) 153-160. 

The potential of regioselective epoxide opening is shown in the ex-chiral-pool synthesis of thromboxane B2 from levoglucosan via epoxide opening as the key step. 

The target molecule is 2-hydroxymethyl-4-methoxy-3,7-dioxabicyclo[4.3.0]nonan-8-one (15), a key intermediate in several synthetic routes to thromboxane B2 8. The sequence9 begins with levoglucosan (9) in which the pyranose chair of D-glucose is conformationally locked by 1,6-etherification. Tosylation occurs chemoselectively at the unhindered positions (C-2 and -4). 

To determine the relevance of in vitro results to clinical setting, Srivastava extended his previous in vitro study (27) to seven healthy female volunteers, who received 5 g of fresh ginger daily for one week. The serum thromboxane activity (thromboxane B2 formation) at baseline was not significantly different compared to that obtained after one week of ginger administration. There were also no evidence of ecchymosis or reports of unusual bleeding episodes (34). 

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