06 Jan 10:12
by Jing, Wang
Tetrodotoxin and congeners are specific voltage-gated sodium channel blockers that exhibit remarkable anesthetic and an-algesic effects. Here, we present a scalable asymmetric synthesis of TTX and 9-epiTTX from the abundant chemical feed-stock furfuryl alcohol. The optically pure cyclohexane skeleton was assembled via a stereoselective Diels-Alder reaction. The dense heteroatom substituents were established sequentially by a series of functional group interconversions on highly oxygenated cyclohexane frameworks, including a chemoselective cyclic anhydride opening, and a decarboxylative hydrox-ylation. An innovative SmI2-mediated concurrent fragmentation, an oxo-bridge ring opening and ester reduction followed by an Upjohn dihydroxylation delivered the highly oxidized skeleton. Ruthenium-catalyzed oxidative alkyne cleavage and formation of the hemiaminal and orthoester under acidic conditions enabled the rapid assembly of TTX, anhydro-TTX, 9-epiTTX, and 9-epi lactone-TTX.
01 Sep 08:47
by Fabien, Gagosz
Direct C-H bond functionalization is a useful strategy for the straightforward formation of C-C and C-Heteroatom bonds. In the present work, a unique approach for the challenging electrophilic Au-catalyzed alpha-C-H bond functionalization of tertiary amines is presented. Electronic, steric and conformational synergistic effects exerted by the use of a malonate unit in the substrate were key to the success of this transformation. This new reactivity was applied to the synthesis of tetrahydro-g-carboline products which, under oxidative conditions, could be converted into valuable structural motifs found in bioactive alkaloid natural products
31 May 05:23
by Joshua B. Cox,
Alex A. Kellum,
Yiwen Zhang,
Bo Li,
Amos B. Smith
The introduction of remote stereochemistry via successive Type I Anion Relay Chemistry (ARC) coupling of commercially available enantioenriched epoxides has enabled a 20-step total synthesis of (−)-bastimolide A. The streamlined assembly and manipulation of ARC products demonstrates a versatile approach that could be leveraged toward other polyhydroxylated macrolides
Abstract
A highly convergent total synthesis of (−)-bastimolide A (1), a polyhydroxy antimalarial macrolide, has been achieved via a longest linear sequence of twenty steps from commercially available glycidyl ethers. Type I Anion Relay Chemistry (ARC) coupling tactics enable rapid construction of the molecule's 1,5-polylol backbone. A late-stage B-alkyl Suzuki–Miyaura union and an Evans-modified Mukaiyama macrolactonization generate the forty-membered Z-α,β-unsaturated macrocyclic lactone.
31 May 05:22
by Kai Wu,
Jacopo Tessarolo,
Ananya Baksi,
Guido H. Clever
Integrative self-assembly of PdII cations with an enantiopure helicene-based ligand and non-chiral but emissive fluorenone ligands yields a series of Pd2L2L′2 heteroleptic coordination cages, showing circularly polarized luminescence (CPL) from the non-chiral moiety. Modulation of the chiroptical properties is achieved by ligand modification or guest binding, achieving an up to 4-fold enhancement of CPL intensity.
Abstract
Multicomponent metallo-supramolecular assembly allows the rational combination of different building blocks. Discrete multifunctional hosts with an accessible cavity can be prepared in a non-statistical fashion. We employ our shape-complementary assembly (SCA) method to achieve for the first time integrative self-sorting of heteroleptic PdII cages showing guest-tunable circularly polarized luminescence (CPL). An enantiopure helicene-based ligand (M or P configuration) is coupled with a non-chiral emissive fluorenone-based ligand (A or B) to form a series of Pd2L2L′2 assemblies. The modular strategy allows to impart the chiral information of the helicenes to the overall supramolecular system, resulting in CPL from the non-chiral component. Guest binding results in a 4-fold increase of CPL intensity. The principle offers potential to generate libraries of multifunctional materials with applications in molecular recognition, enantioselective photo-redox catalysis and information processing.
26 May 08:28
by Anqiao Zhu, Yu Sun, Jingru Lai, Ziyan Chen, Xiaoli Bu, Yan-Ni Yue, Mengtao Ma, and Fei Xue
The Journal of Organic Chemistry
DOI: 10.1021/acs.joc.2c00544
04 Mar 06:34
by Janine Cossy,
Peter Polák
The importance of O/N-glycosides as biologically active compounds cannot be overstated. This study is focused on the functionalization of glycals and ribals at the C2 position with alkyl, vinyl, aryl, heteroaryl and strained ring substituents. The functionalized glycals and ribals were transformed into 2-C-deoxyglycosides and 2’-C-deoxynucleosides. The application to the synthesis of an analogue of cladribine and clofarabine is described.
Abstract
The synthesis of 2-C-glycals and 2-C-ribals was achieved in good yields using a nickel-catalyzed cross-coupling between 2-iodoglycals and 2-iodoribal respectively and Grignard reagents. The prepared 2-C-glycals and ribals were then transformed into 2-C-2-deoxyglycosides, 2-C-diglycosides and 2’-C-2’-deoxynucleosides. The developed method was applied to the synthesis of a 2-chloroadenine
2’-deoxyribonucleoside – a structural analogue of cladribine (Mavenclad®, Leustatin®) and clofarabine (Clolar®, Evoltra®), two compounds used in the treatment of relapsing-remitting multiple sclerosis and hairy cell leukemia.
05 Feb 03:38
by Priyambada Prusty, Subramanian Jambu, and Masilamani Jeganmohan
Organic Letters
DOI: 10.1021/acs.orglett.1c03905
31 Jan 20:30
by Keary, Engle
We report a redox-neutral catalytic coupling of nitroalkanes and unactivated alkenes that proceeds by a directed carbopalladation mechanism. The reaction is uniquely enabled by the combination of PdI2 as the precatalyst and HFIP solvent. Structurally complex nitroalkane products, including nitro-containing carbo- and heterocycles, are prepared under operationally convenient conditions without the need for toxic or corrosive reagents. Deuterium labeling experiments and isolation of a catalytically relevant intermediate shed light on the reaction mechanism. By taking advantage of different catalytic activation modes, we demonstrate orthogonal methods for site-selective functionalization of a polyfunctional nitroalkyl ketone.
21 Jan 02:02
by L. Reginald Mills, David Gygi, Jacob R. Ludwig, Eric M. Simmons, Steven R. Wisniewski, Junho Kim, and Paul J. Chirik
ACS Catalysis
DOI: 10.1021/acscatal.1c05586
05 Jan 18:28
by Jian-Qiang Chen, Xiaodong Tu, Binyan Qin, Shaoxin Huang, Jun Zhang, and Jie Wu
Organic Letters
DOI: 10.1021/acs.orglett.1c04082
12 Nov 06:28
Spectroscopy deciphers censored passages in 200-year-old letters between last French queen and the man rumoured to be her lover