79060-23-4Relevant academic research and scientific papers
5-Formyl- and 5-Carboxydeoxycytidines Do Not Cause Accumulation of Harmful Repair Intermediates in Stem Cells
Rahimoff, René,Kosmatchev, Olesea,Kirchner, Angie,Pfaffeneder, Toni,Spada, Fabio,Brantl, Victor,Müller, Markus,Carell, Thomas
, p. 10359 - 10364 (2017)
5-Formyl-dC (fdC) and 5-carboxy-dC (cadC) are newly discovered bases in the mammalian genome that are supposed to be substrates for base excision repair (BER) in the framework of active demethylation. The bases are recognized by the monofunctional thymine DNA glycosylase (Tdg), which cleaves the glycosidic bond of the bases to give potentially harmful abasic sites (AP-sites). Because of the turnover of fdC and cadC during cell state transitions, it is an open question to what extent such harmful AP-sites may accumulate during these processes. Here, we report the development of a new reagent that in combination with mass spectrometry (MS) allows us to quantify the levels of AP-sites. This combination also allowed the quantification of β-elimination (βE) products, which are repair intermediates of bifunctional DNA glycosylases. In combination with feeding of isotopically labeled nucleosides, we were able to trace the intermediates back to their original nucleobases. We show that, while the steady-state levels of fdC and cadC are substantially increased in Tdg-deficient cells, those of both AP- and βE-sites are unaltered. The levels of the detected BER intermediates are 1 and 2 orders of magnitude lower than those of cadC and fdC, respectively. Thus, neither the presence of fdC nor that of cadC in stem cells leads to the accumulation of harmful AP- and βE-site intermediates.
Stereocontrolled Synthesis of Tetrafluoropentanols: Multivicinal Fluorinated Alkane Units for Drug Discovery
Bentler, Patrick,Erdeljac, Nathalie,Bussmann, Kathrin,Ahlqvist, Marie,Knerr, Laurent,Bergander, Klaus,Daniliuc, Constantin G.,Gilmour, Ryan
supporting information, p. 7741 - 7745 (2019/09/03)
A stereodivergent synthesis of four diastereomeric 2,3,4,5-tetrafluoropentanols is disclosed. X-ray crystallographic analysis reveals conformations that manifest sequential stereoelectronic gauche effects (σC-H/C → σC-F*), thereby generating topological diversity via subtle C(sp3)-H to C(sp3)-F exchange. Two representative tetrafluoro arrays have been incorporated into truncated analogues of Gilenya for the management of relapsing remitting multiple sclerosis. These closely similar multivicinal fluoroalkanes have notably different physicochemical profiles and were found to be stable in the presence of human microsomes.
Stereoselective formal synthesis of (-)-fumagillol
Raghavan, Sadagopan,Yelleni, Mahesh Kumar Rao
, p. 4371 - 4379 (2017/07/03)
A formal synthesis of fumagillol, a congener of fumagillin that possesses varied biological activity, is disclosed. Initial attempts at preparing an allylic sulfide via an α-chloro sulfide met with failure. The successful route involves a carbonyl-ene reaction, one-pot stannyl cupration, methylation of resulting alkenyl copper and further Stille-coupling of the alkenyl stannane as the key steps.
Reversal of facial selectivity in a thia-Claisen rearrangement by incorporation of a vinylic bromine substituent
Ellwood, Adam R.,Mortimer, Anne J. Price,Goodman, Jonathan M.,Porter, Michael J.
supporting information, p. 7530 - 7539 (2013/11/06)
Thia-Claisen rearrangements have been carried out using N-benzylpyrrolidine-2-thione and chiral allylic bromides derived from d-mannitol. Introduction of a bromine atom onto the double bond of the allylic bromide reverses the sense of diastereoselectivity in the [3,3]-sigmatropic rearrangement. Density functional theory calculations lead us to rationalise the observed selectivity in terms of a Cieplak effect.
A simple and efficient stereoselective synthesis of (-)-cleistenolide
Vijaya Kumar,Suresh Babu,Madhusudana Rao
scheme or table, p. 1823 - 1825 (2012/05/04)
A simple and straightforward stereoselective synthesis of α,β-unsaturated δ-lactone, (-)-cleistenolide has been accomplished in 10 steps in an overall yield of 19%, starting from inexpensive and commercially available starting materials, respectively. This linear synthesis utilizes Sharpless asymmetric dihydroxylation, sulfur ylide mediated epoxide opening followed by ring-closing metathesis (RCM) for the formation of six-membered lactone ring as the key step sequence.
Iterative asymmetric allylic substitutions: Syn- and anti-1,2-diols through catalyst control
Park, Jin Kyoon,McQuade, D. Tyler
supporting information; experimental part, p. 2717 - 2721 (2012/04/17)
A copper-catalyzed asymmetric allylic boronation (AAB) gives access to syn- and anti-1,2-diols. The method facilitates an iterative strategy for the preparation of polyols (see scheme), such as the fully differentiated L-ribo-tetrol and protected D-arabin
Ring-closing metathesis (RCM) based synthesis of the macrolactone core of amphidinolactone A
Mohapatra, Debendra K.,Pattanayak, Manas R.,Das, Pragna P.,Pradhan, Tapas R.,Yadav
scheme or table, p. 5630 - 5632 (2011/09/16)
A convergent synthesis of the macrolactone core of amphidinolactone A has been achieved, in a 10 step linear sequence with 32% overall yield, through a ring-closing metathesis reaction as the macrolactonization step. The RCM precursor was obtained by the
1,2-diastereoselective C-C bond-forming reactions for the synthesis of chiral β-branched α-amino acids
Spangenberg, Thomas,Schoenfelder, Angele,Breit, Bernhard,Mann, Andre
experimental part, p. 6005 - 6018 (2011/02/25)
SN2′ sequences have been employed for the synthesis of β-branched α-amino acids using 1,2-diastereocontrol for forming C-C bonds. An oxazolidine fragment derived from Garner's aldehyde provides the handle for facial discrimination and acts as a
An improved two-step synthetic route to primary allylic alcohols from aldehydes
Liu, Zheng,Gong, Yaqiong,Byun, Hoe-Sup,Bittman, Robert
experimental part, p. 470 - 475 (2010/06/14)
An improved two-step synthetic route to allylic alcohols from aldehydes has been developed. A modification of the HWE reaction in H2O-2-PrOH (1 : 1) and a convenient protocol to prepare AlH3 in THF from LiAlH 4 and n-BuBr are the key factors in the improvement.
Stereoselective Reformatskii-Claisen rearrangement: Synthesis of 2′,3′-dideoxy-6′,6′-difluoro-2′-thionucleosides
Zheng, Feng,Zhang, Xingang,Qing, Feng-Ling
scheme or table, p. 1505 - 1507 (2009/09/06)
A new approach for the stereoselective synthesis of 2′,3′- dideoxy-6′,6′-difluoro-2′-thionucleosides, analogues of highly bioactive L-OddC and 3TC, has been developed via TMSCl/pyridine induced stereoselective Reformatskii-Claisen rearragement of secondar
