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Synthesis of 1L-chiro-inositol 2,3,5-trisphosphorothioate, the first partial agonist at the platelet myo-inositol 1,4,5-trisphosphate receptor. 1994

C Liu, and J al-Hafidh, and J Westwick, and B V Potter
School of Pharmacy & Pharmacology, University of Bath, U.K.

The synthesis of L-chiro-inositol 2,3,5-trisphosphorothioate, a novel analogue of the second messenger D-myo-inositol 1,4,5-trisphosphate has been accomplished from the natural product L-quebrachitol. Phosphitylation of (-)-1L-1,4,6-tri-O-benzoyl-chiro-inositol obtained from L-quebrachitol followed by sulfoxidation of the products gave (-)-1L-1,4,6-tri-O-benzoyl-chiro-inositol 2,3,5-tris[di(2-cyanoethyl) phosphorothioate], which was deblocked using sodium in liquid ammonia to give 1L-(-)-chiro-inositol 2,3,5-trisphosphorothioate. 1L-chiro-Inositol 2,3,5-trisphosphorothioate is a partial agonist in the release of intracellular Ca2+ from saponin-permeabilised platelets and is both a key tool for pharmacological dissection of the polyphosphoinositide pathway of cellular signalling and a lead compound for the design of small molecule Ins(1,4,5)P3 receptor antagonists.

UI MeSH Term Description Entries
D009946 Organothiophosphorus Compounds Compounds containing carbon-phosphorus bonds in which the phosphorus component is also bonded to one or more sulfur atoms. Many of these compounds function as CHOLINERGIC AGENTS and as INSECTICIDES. Compounds, Organothiophosphorus
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D001792 Blood Platelets Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D015220 Calcium Channels Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. Ion Channels, Calcium,Receptors, Calcium Channel Blocker,Voltage-Dependent Calcium Channel,Calcium Channel,Calcium Channel Antagonist Receptor,Calcium Channel Antagonist Receptors,Calcium Channel Blocker Receptor,Calcium Channel Blocker Receptors,Ion Channel, Calcium,Receptors, Calcium Channel Antagonist,VDCC,Voltage-Dependent Calcium Channels,Calcium Channel, Voltage-Dependent,Calcium Channels, Voltage-Dependent,Calcium Ion Channel,Calcium Ion Channels,Channel, Voltage-Dependent Calcium,Channels, Voltage-Dependent Calcium,Voltage Dependent Calcium Channel,Voltage Dependent Calcium Channels
D015290 Second Messenger Systems Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. Intracellular Second Messengers,Second Messengers,Intracellular Second Messenger,Messenger, Second,Messengers, Intracellular Second,Messengers, Second,Second Messenger,Second Messenger System,Second Messenger, Intracellular,Second Messengers, Intracellular,System, Second Messenger,Systems, Second Messenger
D015544 Inositol 1,4,5-Trisphosphate Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. 1,4,5-InsP3,Inositol 1,4,5-Triphosphate,Myo-Inositol 1,4,5-Trisphosphate,1,4,5-IP3,Myoinositol 1,4,5-Triphosphate
D053496 Inositol 1,4,5-Trisphosphate Receptors Intracellular receptors that bind to INOSITOL 1,4,5-TRISPHOSPHATE and play an important role in its intracellular signaling. Inositol 1,4,5-trisphosphate receptors are calcium channels that release CALCIUM in response to increased levels of inositol 1,4,5-trisphosphate in the CYTOPLASM. Inositol 1,4,5-Triphosphate Receptor,Inositol 1,4,5-Triphosphate Receptors,Inositol 1,4,5-Trisphosphate Receptor,1,4,5-INTP Receptor,INSP3 Receptor,INSP3 Receptor Type 1,INSP3 Receptor Type 2,INSP3 Receptor Type 3,IP3 Receptor,Inositol 1,4,5-trisphosphate Receptor Subtype 3,Inositol 1,4,5-trisphosphate Receptor Type 1,Inositol 1,4,5-trisphosphate Receptor Type 2,Inositol 1,4,5-trisphosphate Receptor Type 3,Inositol Triphosphate Receptor,Inositol-1,4,5-Triphosphate Receptor,Receptor, Inositol-1,4,5-triphosphate,Type 1 Inositol 1,4,5-trisphosphate Receptor,Type 3 Inositol 1,4,5-trisphosphate Receptor,Receptor, INSP3,Receptor, IP3,Receptor, Inositol Triphosphate,Triphosphate Receptor, Inositol

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