No abstract

Displacement of chloride from CpFe-(CO)2CH2CI by HPEt2 followed by deprotonation yields the new V-phosphinomethyl complex CpFe(CO)2(?71-CH2PEt2) (2). Suprisingly, thermolysis of this complex does not lead either to the CO insertion product acyl 7 or to the cyclic CO loss product CpFe(CO)1(?72 56-CH2PEt2) (5). Coordination of the phosphorus to the iron atom occurs only upon photolysis to yield the rf species 5, which spectroscopic data and molecular weight data confirm is a cyclic monomer. Thermolysis of this complex fails to yield characterizable product. Protonolysis of the Fe-C bond occurs with HBF4-OMe2, yielding CpFe(CO)2PMeEt2+.Many examples of transition-metal complexes containing the CH2PR2 ligand have been reported in the literature.

Mealtime pramlintide (PRAM) and insulin (INS) reduce postprandial glucose excursions, mimics natural pancreas physiology and improves glycemic control. Due to differences in physico-chemical characteristics of PRAM and INS, mixing these two products can cause precipitation. Xeris has developed novel room temperature stable co-formulations to overcome precipitation, simplify dose administration and reduce injection burden. Streptozotocin (65 mg/kg) treated SD rats were given co-formulations of PRAM and Regular Insulin (RI) or Lispro Insulin (LISPRO) as a single injection and compared with dual injection of commercial Symlin, Humulin, or Humalog. Blood samples were evaluated for plasma glucose and PK. A sparse sampling PK scheme resulted in ∼30% CV for glucose values. Mean glucose profiles with reductions in glucose AUC by treatment (efficacy). PRAM-INS single injection co-formulations showed comparable efficacy and PK profiles to two injection commercial products. Consistent with PRAM's known pharmacological action, there was no glucose lowering with PRAM alone. These results support clinical development of room temperature stable PRAM-INS co-formulations. Disclosure S. Thohan: None. W.T. Hu: None. M.J. Donovan: None. S.J. Prestrelski: Employee; Self; Xeris Pharmaceuticals, Inc. M.S. Choi: None. D.M. Hester: None.

UV photolysis of the title compound yields FeCp(CO),PEt,Me+ by (3-elimination from the phosphonium methyl moiety with evidence for an intermediate q2-phosphinomethanide metal hydride complex.Elimination of a P-hydrogen atom from metal alkyls is a facile route to the formation of metal-alkene hydride complexes. Pannell proposed the first observation of (3-hydrogen elimination from silylmethyl complexes in the photochemical rearrangement of the dimethylsilylmethyl group in FeCp-( C0)2CH2SiHMe2, 1 In studying a similar rearrangement process, Wrighton et al. reported intermediates which contained both q2-silene and hydride ligands.2 More recently, Tilley prepared a transition metal stabilized q2-silene hydride complex prepared via (3-hydrogen elimination from a silylmethyl ligand.3 We recently reported the synthesis of an y 1-phosphinomethanide complex (ql-CH2PR2) and its controlled photochemical conversion to the q2-CH2PR2 form.4 In this communication we report that the precursor for the q t complex, FeCp(CO),CH2PHEt2+ undergoes a photochemical rearrangement which provides the first evidence of hydrogen elimination from a 13-phosphonium to form ; 1 coordinated $--CH2PR2 structure aRoom temperature photolysis of a bright yellow CH2C12 or CD2CI2 5olution of phosphonium cation 1 with a tungsten filament lamp provides the rearranged phosphine complex FeCp(CO),PEt,Me+ 3 in quantitative yield by NMR and in ?4% isolated yield. When the photolysis is carried out under CO (2 atm) the 31P{IH} NMR spectrum shows clean replacement of the single starting material resonance at 6 37.87 with a new resonance at 6 53.17 which is assigned to the product. The 1H NMR spectrum shows clean formation of

Insulin therapy is the primary treatment option for patients with type 1 and 2 diabetes. Despite considerable advances in insulin chemistry, delivery, and pharmacology, only a small percentage of diabetic patients achieve near normal glycemic levels. Xeris has developed novel room temperature stable insulin formulations that may offer duration of efficacy advantages over commercially available options. Streptozotocin (65 mg/kg) treated SD rats were given co-formulations of PRAM and Regular Insulin (RI) or Lispro Insulin (LISPRO) as a single injection and compared with dual injection of commercial Symlin, Humulin, or Humalog. Blood samples were evaluated for plasma glucose and PK. A sparse sampling PK scheme resulted in ∼30% CV for glucose values. Mean glucose profiles with reductions in glucose AUC by treatment (efficacy). XeriSol™ insulins showed comparable efficacy and pharmacokinetic profiles commercial products with up to 4 hours of glycemic control. Xerisol formulations of Insulin and Lispro showed trends for lower sustained means (30-240 min) for glucose levels and slightly longer half-lives than comparative doses of commercial Humulin and Humalog. Disclosure S. Thohan: None. M.J. Donovan: None. W.T. Hu: None. M.S. Choi: None. D.M. Hester: None. S.J. Prestrelski: Employee; Self; Xeris Pharmaceuticals, Inc.