We recently reported the incorporation of diazirine photo-cross-linkers onto the O-GlcNAc posttranslational modification in mammalian cells, enabling the identification of binding partners of O-GlcNAcylated proteins. Unfortunately, the syntheses of the diazirine-functionalized substrates have exhibited inconsistent yields. We report a robust and stereoselective synthesis of cell-permeable GlcNAc-1-phosphate esters based on the use of commercially available bis(diisopropylamino)chlorophosphine. We demonstrate this approach for two diazirine-containing GlcNAc analogues, and we report the cellular incorporation of these compounds into glycoconjugates to support photo-cross-linking applications.
Acetylglucosamine , Phosphates , Animals , Diazomethane , Glycoconjugates , Proteins
Echitamine (1) and akuammiline (2) are representative members of a fascinating class of monoterpenoid indole alkaloids. We report the syntheses of 2 and its congener deacetylakuammiline (3). The azabicyclo[3.3.1]nonane motif was assembled through silver-catalyzed internal alkyne cyclization, and one-pot C-O bond cleavage/C-N bond formation furnished the pentacyclic scaffold. Compound 3 then served as a common intermediate for preparing a series of structurally diverse and synthetically challenging congeners including 1. A position-selective Polonovski-Potier reaction followed by formal N-4 migration built the core of N-demethylechitamine (4) and 1. An alternative route featuring Meisenheimer rearrangement gave 4 as well. Oxidation of the alcohol within 3 gave rhazimal (5), which underwent tandem indolenine hydrolysis, hemiaminalization, and hemiketalization to form rhazicine (6). A sequence of N,O-ketalization and reductive amination secured the chemoselectivity of N-methylation, leading to pseudoakuammigine (7).
Alkaloids/chemical synthesis , Molecular Structure , Stereoisomerism
A Lewis acid catalyzed Nazarov-type cyclization of arylvinylcarbinol has been developed for the asymmetric synthesis of carbotetracyclic core of merosesquiterpenes. The reaction works only in the presence of 2 mol % of Sn(OTf)2 and Bi(OTf)3 in dichloroethane under elevated temperature. The methodology offers the synthesis of a variety of enantioenriched arylvinylcarbinols from commercially available (3aR)-sclareolide 9 in six steps with an eventual concise total synthesis of marine sesquiterpene quinol, akaol A (1a).
Diterpenes/chemistry , Lewis Acids/chemistry , Methanol/chemistry , Sesquiterpenes/chemical synthesis , Catalysis , Methanol/analogs & derivatives , Molecular Structure , Sesquiterpenes/chemistry , Stereoisomerism
Total synthesis of (±)-taiwaniaquinol F (1a) has been accomplished via an efficient Lewis acid-catalyzed Nazarov-type cyclization of aryldiallylcarbinols (±)-2e derived from safranal 7. The methodology works under mild conditions using only 2 mol % of metal triflate as catalyst to afford a previously unknown carbotricyclic core sharing an olefin functionality in excellent yield. The aforementioned methodology also offers enough flexibility to complete the total syntheses of various taiwaniaquinoids, including (±)-taiwaniaquinone H (1d), (±)-dichroanone (1e), (±)-5-epi-taiwaniaquinone G (ent-1h), and (±)-taiwaniaquinol B (1b).
Diterpenes/chemical synthesis , Diterpenes/chemistry , Molecular Conformation , Stereoisomerism
We report a catalytic stereoconvergent construction of vicinal all-carbon quaternary centers via double stereoablative enantioselective alkylation of a mixture having racemic and meso diastereomers of esters to afford exceptional levels of diastereo- (up to 17 : 1) and enantioselectivity (up to >99% ee). The strategy offers an efficient and general approach to dimeric cyclotryptamine alkaloids sharing a labile C(3a)-C(3a') σ-bond in the hexahydropyrroloindoline core.
A methodology involving a "transition metal-free" intramolecular biaryl-coupling of o-halo-N-arylbenzylamines has been developed in the presence of potassium tert-butoxide and an organic molecule as catalyst. The reaction appears to proceed through KO(t)Bu-promoted intramolecular homolytic aromatic substitution (HAS). Interestingly, this biaryl coupling also works in the presence of potassium tert-butoxide as sole promoter. On extending our approach further, we found that N-acyl 2-bromo-N-arylbenzylamines undergo a one-pot N-deprotection/biaryl coupling followed by oxidation, thus offering an expeditious route to the phenanthridine and benzo[c]phenanthridine skeletons. The strategy has been applied to a concise synthesis of Amaryllidaceae alkaloids viz. oxoassoanine (1b), anhydrolycorinone (1d), 5,6-dihydrobicolorine (2d), trispheridine (2b), and benzo[c]phenanthridines alkaloids dihydronitidine (3b), dihydrochelerythidine (3d), dihydroavicine (3f), nornitidine (3h), and norchelerythrine (3j).
Benzophenanthridines/chemical synthesis , Butanols/chemistry , Phenanthridines/chemical synthesis , Pyrroles/chemical synthesis , Benzophenanthridines/chemistry , Catalysis , Molecular Structure , Phenanthridines/chemistry , Pyrroles/chemistry
An intramolecular-dehydrogenative-coupling (IDC) using "transition-metal-free" oxidation conditions has been achieved to synthesize a variety of 2-oxindoles bearing an all-carbon quaternary stereogenic center at the benzylic position. The methodology involves a one-pot C-alkylation of ß-N-arylamido esters (3, 6) with alkyl halides using potassium tert-butoxide concomitant with a dehydrogenative coupling. A radical-mediated pathway has been tentatively proposed for the oxidative process.
