Structural Tracking of the Potassium‐Mediated Magnesiation of Anisole

Abstract

Although a number of infants with maternal uniparental disomy of chromosome 16 (upd(16)mat) have been reported, the evidence for imprinting on chromosome 16 is not yet conclusive. To test the hypothesis that upd(16)mat has a distinct phenotype, which would support the existence of imprinted gene(s) on chromosome 16, statistical analysis was performed on a large series (n = 83) of mosaic trisomy 16 cases with molecular determination of uniparental disomy status. The incidence of upd(16)mat was 40%, which is consistent with the expected one third from random chromosome loss during trisomy rescue (P = 0.262). In pairwise comparisons, upd(16)mat was found to be associated with fetal growth restriction (P = 0.029) and with increased risk of major malformation (RR = 1.43; P = 0.053). Regression modeling showed that the effect of upd(16)mat on fetal/neonatal weight and malformation is independent of the degree of trisomy detected in the fetus. Regression modeling to control for the degree of trisomy detected in the placenta was not possible due to limited sample size. We conclude that upd(16)mat is associated with more severe growth restriction, and possibly, with higher risk of malformation. Our hypothesis is that imprinted gene(s) exist on chromosome 16 and that abnormal expression of these gene(s) in upd(16)mat cells during development results in decreased cell proliferation. Although we do not advocate prenatal testing for upd(16), studies on the long‐term outcome of upd(16)mat neonates is necessary for counseling purposes. © 2002 Wiley‐Liss, Inc.

Magnesium‐Mediated Benzothiazole Activation: A Room‐Temperature Cascade of CH Deprotonation, CC Coupling, Ring‐Opening, and Nucleophilic Addition Reactions

“…Furthermore, the presence of a Bu group in B suggests that deprotonation appears to be the rate‐determining step of this process. The formation of B can be rationalized similarly as proposed for A (Scheme ), where now as a result of the lower temperature, a single btz molecule is deprotonated (with 2 acting as a mono‐amido base, leaving the Bu group bonded to Mg)19 with a subsequent similar fast CC coupling and intramolecular ring‐opening reaction that is then terminated by the Bu nucleophilic addition to the CN bond (see Scheme S1 in the Supporting Information). In this case, the intramolecular deprotonation (step e, Scheme ) does not occur, probably because it would generate a highly unstable carbanion with a negative charge α to an amido nitrogen atom 20.…”

Alkali‐Metal‐Mediated Magnesiations of an N‐Heterocyclic Carbene: Normal, Abnormal, and “Paranormal” Reactivity in a Single Tritopic Molecule

“…THF could be af actor in the lack of at emplate effect in the metalation as this lone-pair donor can compete for metal coordination sites and deaggregate the (KNMgN) 6 24 atom ring structure.S ignificantly donor-solvated potassium magnesiate [(PMDETA)KMg(TMP) 2 (CH 2 SiMe 3 )] is known to deprotonate aromatic substrates kinetically through TMP. [20] Thec rystalline 2 exhibits an infinite,z ig-zag chain structure ( Figure 1 [19] is consistent with as ingle compound of empirical formula [{KMg(TMP) 2 (IPr À )} n ]( 3), where IPr is deprotonated at C4. [21] Most compelling is that the 1 HDOSY NMR [22] [19] Significantly,t his formulation is consistent with at emplate metalation through nBu basicity (butane loss), thus matching other reactions of 1 in non-donor media.…”

Magnesium‐Mediated Benzothiazole Activation: A Room‐Temperature Cascade of CH Deprotonation, CC Coupling, Ring‐Opening, and Nucleophilic Addition Reactions

“…Furthermore, the presence of a Bu group in B suggests that deprotonation appears to be the rate-determining step of this process. The formation of B can be rationalized similarly as proposed for A (Scheme 2), where now as a result of the lower temperature, a single btz molecule is deprotonated (with 2 acting as a mono-amido base, leaving the Bu group bonded to Mg) [19] with a subsequent similar fast CÀC coupling and intramolecular ring-opening reaction that is then terminated by the Bu nucleophilic addition to the C = N bond (see Scheme S1 in the Supporting Information). In this case, the intramolecular deprotonation (step e, Scheme 2) does not occur, probably because it would generate a highly unstable carbanion with a negative charge a to an amido nitrogen atom.…”