The role of the C(8) gem-dimethyl group in the A-ring of bryostatin 1 has been examined through chemical synthesis and biological evaluation of a new analogue. Assays for biological function using U937, K562, and MV4-11 cells as well as the profiles for downregulation of PKC isozymes revealed that the presence of this group is not a critical determinant for the unique pattern of biological activity of bryostatin.
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http://dx.doi.org/10.1016/j.bmcl.2012.04.073 | DOI Listing |
Science
February 2024
Department of Chemistry, University College London, London WC1H 0AJ, UK.
Coenzyme A (CoA) is essential to all life on Earth, and its functional subunit, pantetheine, is important in many origin-of-life scenarios, but how pantetheine emerged on the early Earth remains a mystery. Earlier attempts to selectively synthesize pantetheine failed, leading to suggestions that "simpler" thiols must have preceded pantetheine at the origin of life. In this work, we report high-yielding and selective prebiotic syntheses of pantetheine in water.
View Article and Find Full Text PDFOrg Biomol Chem
July 2021
Department of Chemistry, Indian Institute of Science Education and Research (IISER) Pune, Dr Homi Bhabha Road, Pune 411008, India and Chemistry Department and CAMOST, Indian Institute of Science Education and Research (IISER) Tirupati, Karkambadi Road, Mangalam, Tirupati 517507, India.
The flexible backbone of aminoethylglycine (aeg) PNA upon substitution becomes sterically constrained to enable conformational pre-organization for preferential binding to DNA or RNA. The bulky gem-dimethyl (gdm) substituent on carbons adjacent to the t-amide sidechain either at Cα (glycyl) or Cβ/Cγ (aminoethylene) sides may influence the Z/E rotamer ratio arising from a restricted rotation around the t-amide bond. Employing 2D NMR (NOESY), it is shown here that the Cα-gdm-PNA-T monomer exhibits exclusively the Z-rotamer, while the Cβ-gdm-PNA-T monomer shows only the E-rotamer.
View Article and Find Full Text PDFDalton Trans
June 2019
Key Laboratory of Engineering Plastics and Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. and CAS Research/Education Center for Excellence in Molecular Sciences and International School, University of Chinese Academy of Sciences, Beijing 100049, China.
Six types of 2,8-bis(imino)-7,7-dimethyl-5,6-dihydroquinoline, 2-(ArN[double bond, length as m-dash]CMe)-8-(ArN)-7,7-MeCHN (Ar = 2,6-MeCHL1, 2,6-EtCHL2, 2,6-PrCHL3, 2,4,6-MeCHL4, 2,6-Et-4-MeCHL5, 2,4,6-BuCHL6), distinguishable by their steric and electronic profile, are described that can readily undergo complexation with cobaltous chloride to form their corresponding LCoCl chelates, Co1-Co6. The molecular structures of Co2 and Co3 reveal square pyramidal geometries with ring puckering a feature of the gem-dimethyl section of their unsymmetrical N,N,N'-ligands. On activation with either methylaluminoxane (MAO) or modified methylaluminoxane (MMAO), all the cobalt complexes exhibited exceptionally high activities for ethylene polymerization with levels reaching up to 1.
View Article and Find Full Text PDFOrg Lett
September 2014
Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, U.K.
An enantioselective synthesis of the AB ring system common to the majority of the Schisandra nortriterpenoid natural products is reported. Key steps include a stereospecific ring opening of a trisubstituted epoxide and the use of a β-lactone to enable installation of the gem-dimethyl functionality of the B ring. An acetalization strategy played a key role in a late-stage biomimetic AB ring bicyclization.
View Article and Find Full Text PDFBioorg Med Chem Lett
June 2012
University of Utah, Department of Chemistry, 315 South 1400 East, RM 2020, Salt Lake City, UT 84112, USA.
The role of the C(8) gem-dimethyl group in the A-ring of bryostatin 1 has been examined through chemical synthesis and biological evaluation of a new analogue. Assays for biological function using U937, K562, and MV4-11 cells as well as the profiles for downregulation of PKC isozymes revealed that the presence of this group is not a critical determinant for the unique pattern of biological activity of bryostatin.
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