N-Heteroarylation of Optically Pure α-Amino Esters using the Pd-PEPPSI-IPent -o-picoline Pre-Catalyst.

A robust, mild, and efficient method for the Pd-catalyzed N-heteroarylation of optically pure α-amino esters was developed. Dichloro[1,3-bis(2,6-di-3-pentylphenyl)imidazol-2-ylidene](o-picoline)palladium(II) (Pd-PEPPSI-IPent -o-picoline; PEPPSI=pyridine enhanced pre-catalyst preparation, stabilization, and initiation) was shown to effectively couple a variety of amino acids as the tert-butyl ester with heteroaryl chlorides in high yields and with excellent stereoretention of the acidic proton adjacent to the ester. Control experiments revealed that racemization is base-mediated, with no evidence of Pd-mediated β-hydride elimination when using Pd-PEPPSI-IPent , and that racemization occurs only after the product is formed, that is, the non-arylated starting amino ester does not deprotonate under our reaction conditions.

Solvent choice and kinetic isotope effects (KIEs) dramatically alter regioselectivity in the directed ortho metalation (DoM) of 1,5-dichloro-2,4-dimethoxybenzene.

The regioselective formation of the 6-lithio derivative of 1,5-dichloro-2,4-dimethoxybenzene (i.e., 12) by directed ortho metalation (DoM) with nBuLi in THF is described.

[(IPent)PdCl2(morpholine)]: a readily activated precatalyst for room-temperature, additive-free carbon-sulfur coupling.

A series of new, easily activated NHC-Pd(II) precatalysts featuring a trans-oriented morpholine ligand were prepared and evaluated for activity in carbon-sulfur cross-coupling chemistry. [(IPent)PdCl2(morpholine)] (IPent=1,3-bis(2,6-di(3-pentyl)phenyl)imidazol-2-ylidene) was identified as the most active precatalyst and was shown to effectively couple a wide variety of deactivated aryl halides with both aryl and alkyl thiols at or near ambient temperature, without the need for additives, external activators, or pre-activation steps. Mechanistic studies revealed that, in contrast to other common NHC-Pd(II) precatalysts, these complexes are rapidly reduced to the active NHC-Pd(0) species at ambient temperature in the presence of KOtBu, thus avoiding the formation of deleterious off-cycle Pd(II)-thiolate resting states.

Environmental gestagens activate fathead minnow (Pimephales promelas) nuclear progesterone and androgen receptors in vitro.

Gestagen is a collective term for endogenous and synthetic progesterone receptor (PR) ligands. In teleost fishes, 17α,20β-dihydroxy-4-pregnen-3-one (DHP) and 17α,20β,21-trihydroxy-4-pregnen-3-one (20β-S) are the predominant progestogens, whereas in other vertebrates the major progestogen is progesterone (P4). Progestins are components of human contraceptives and hormone replacement pharmaceuticals and, with P4, can enter the environment and alter fish and amphibian reproductive health.

Room-temperature amination of deactivated aniline and aryl halide partners with carbonate base using a Pd-PEPPSI-IPentCl-o-picoline catalyst.

Current state-of-the-art protocols for the coupling of unreactive amines (e.g., electron-poor anilines) with deactivated oxidative-addition partners (e.

Regioselective cross-coupling of allylboronic acid pinacol ester derivatives with aryl halides via Pd-PEPPSI-IPent.

The cross-coupling reactions of allylboronic acid pinacol ester derivatives with aryl and heteroaryl halides occurred with high selectivity (>97%) at the α-carbon of the allylboron reagent in the presence of Pd-PEPPSI-IPent precatalyst and 5 M KOH in refluxing THF. In the case of trisubstituted allylboronates with different substituents on the olefin, minor olefin geometry isomerization was observed (E/Z ≈ 80/20).

Creating females? Developmental effects of 17α-ethynylestradiol on the mangrove rivulus' ovotestis.

Interest in the occurrence and fate of trace organic contaminants in the aquatic environment and their potential effects on all organisms has increased over the past two decades. Researches on contaminants have included both natural and synthetic estrogenic contaminants, neuroactive pharmaceuticals, and other endocrine disrupting chemicals that are mediated by the androgen and progesterone receptors. Exposure to very low concentrations (ng/L or parts per trillion) of compounds such as 17α-ethynylestradiol (EE(2)), a synthetic estrogen, can affect gonadal development, viability and production of eggs, fertilization rate, and sexual differentiation in fishes.

Progesterone and interferon tau-regulated genes in the ovine uterine endometrium: identification of periostin as a potential mediator of conceptus elongation.

During early pregnancy in ruminants, progesterone (P(4)) and interferon tau (IFNT) act on the endometrium to regulate genes hypothesized to be important for conceptus development and implantation. The present study was conducted to verify several candidate genes (actin alpha-2, smooth muscle, aorta (ACTA2), collagen, type III, alpha-1 (COL3A1), periostin (POSTN), secreted protein acidic cysteine-rich (SPARC), S100 calcium-binding protein A2 (S100A2), STAT5A and transgelin (TAGLN)) regulated by pregnancy, P(4), and/or IFNT in the endometrium determined using a custom ovine cDNA array. S100A2 mRNA was detected primarily in endometrial epithelia and conceptuses.

Progesterone and placentation increase secreted phosphoprotein one (SPP1 or osteopontin) in uterine glands and stroma for histotrophic and hematotrophic support of ovine pregnancy.

Secreted phosphoprotein one (SPP1, osteopontin) may regulate conceptus implantation and placentation. We investigated effects of progesterone (P(4)) and the conceptus on expression and localization of SPP1 in the ovine uterus. Steady-state levels of SPP1 mRNA in the endometrium of unilaterally pregnant ewes did not differ significantly between nongravid and gravid horns within their respective days of pregnancy; however, levels did increase as pregnancy progressed.

Insulin-like growth factor II activates phosphatidylinositol 3-kinase-protooncogenic protein kinase 1 and mitogen-activated protein kinase cell Signaling pathways, and stimulates migration of ovine trophectoderm cells.

IGF-II, a potent stimulator of cellular proliferation, differentiation, and development, regulates uterine function and conceptus growth in several species. In situ hybridization analyses found that IGF-II mRNA was most abundant in the caruncular endometrial stroma of both cyclical and pregnant ewes. In the intercaruncular endometrium, IGF-II mRNA transitioned from stroma to luminal epithelium between d 14 and 20 of pregnancy.

Galectin 15 (LGALS15) functions in trophectoderm migration and attachment.

Galectin 15 (LGALS15) is expressed specifically by the endometrial luminal epithelium (LE) of the ovine uterus in concert with blastocyst growth, elongation, and implantation. LGALS15 contains a predicted carbohydrate recognition domain (CRD) as well as LDV and RGD recognition sequences for integrin binding. Studies tested the hypothesis that LGALS15 is a secreted regulator of blastocyst development, as well as growth, migration, adhesion, and apoptosis of trophoblast.

Galectin 15 (LGALS15): a gene uniquely expressed in the uteri of sheep and goats that functions in trophoblast attachment.

Galectins are a family of secreted animal lectins with biological roles in cell adhesion and migration. In sheep, galectin 15 (LGALS15) is expressed specifically in the endometrial luminal (LE) and superficial glandular (sGE) epithelia of the uterus in concert with blastocyst elongation during the peri-implantation period. The present study examined LGALS15 expression in the uterus of cattle, goats, and pigs.

Endogenous retroviruses regulate periimplantation placental growth and differentiation.

Endogenous retroviruses (ERVs) are fixed and abundant in the genomes of vertebrates. Circumstantial evidence suggests that ERVs play a role in mammalian reproduction, particularly placental morphogenesis, because intact ERV envelope genes were found to be expressed in the syncytiotrophoblasts of human and mouse placenta and to elicit fusion of cells in vitro. We report here in vivo and in vitro experiments finding that the envelope of a particular class of ERVs of sheep, endogenous Jaagsiekte sheep retroviruses (enJSRVs), regulates trophectoderm growth and differentiation in the periimplantation conceptus (embryo/fetus and associated extraembryonic membranes).

Identification of endometrial genes regulated by early pregnancy, progesterone, and interferon tau in the ovine uterus.

During early pregnancy in ruminants, progesterone (P4) from the corpus luteum and interferon tau (IFNT) from the conceptus act on the endometrium to regulate genes important for uterine receptivity and conceptus growth. The use of the uterine gland knockout (UGKO) ewe has demonstrated the critical role of epithelial secretions in regulation of conceptus survival and growth. A custom ovine cDNA array was used to identify alterations in gene expression of endometria from Day 14 cyclic, pregnant, and UGKO ewes (study 1) and from cyclic ewes treated with P4 or P4 with ZK 136,317 antiprogestin and control proteins or IFNT (study 2).