Towards the real didemnaketal A: total syntheses of two C-21 stereoisomers of the proposed didemnaketal A

Two isomers (3 and 4) with a configuration at C-21 opposite to that proposed for didemnaketal A were synthesized through a process in which the longest linear sequence involved 29 steps. Comparative NMR analysis of these isomers and natural didemnaketal A suggests the possibility of misassignments at other stereocenters in the proposed structure of didemnaketal A.     

Convergent assembly of the spiroacetal subunit of didemnaketal B

A highly convergent synthesis of the C9-C28 spiroacetal subunit of didemnaketal B has been accomplished. Assembly of the C9-C15 alkylborate and C16-C21 enol phosphate by means of Suzuki-Miyaura coupling and acid-catalyzed cyclization of the derived dihydroxy enol ether enabled a rapid and efficient construction of the spiroacetal subunit. The C22-C28 side chain was incorporated via Nozaki-Hiyama-Kishi coupling to complete the synthesis.     

Toward the synthesis of didemnaketal B: a convergent synthesis of the C9-C28 subunit

Synthesis of the C9-C28 subunit of didemnaketal B has been developed. This subunit was convergently prepared from four chiral synthons and at the longest linear sequence required 16 steps.     

Didemnaketal A类似物的合成研究──C8-C15中间体的合成

DidemnaketalA是一类具有明显抗艾滋病活性的天然螺环缩酮类化合物^[1],但至今未见有关合成及立体化学研究的报道.为进一步研究这类螺环缩酮类化合物的生理活性,我们开展了侧链简化的类似物(如化合物1)的合成研究.     

Synthesis of the 5-7-6 core of guanacastepenes. Construction of C8 quaternary carbon via the inversion of stereochemistry

[formula: see text] An efficient and unique route to the 5-7-6 core of guanacatepene A (1) is described. The installation of the desired stereochemistry at the C8 position was achieved via the desymmetrization of the cyclohexadienone by reductive ring closure of the seven-membered ring. That the closure of the seven-membered ring produced only the desired isomer is hypothesized to be a result of the more stable trans relationship between the C8 and C11 methyl groups.     

Total Synthesis and Structure Revision of Didemnaketal B

Didemnaketal B, a structurally complex spiroacetal that exhibits potent HIV‐1 protease inhibitory activity, was originally discovered by Faulkner and his colleagues from the ascidian Didemnum sp. collected at Palau. Its absolute configuration was proposed on the basis of degradation/derivatization experiments of the authentic sample. However, our total synthesis of the proposed structure of didemnaketal B questioned the stereochemical assignment made by Faulkner et al. Here we describe in detail our first total synthesis of the proposed structure 2 of didemnaketal B, which features 1) a convergent synthesis of the C7–C21 spiroacetal domain by means of a strategy exploiting Suzuki–Miyaura coupling, 2) an Evans syn‐aldol reaction and a vinylogous Mukaiyama aldol reaction for the assembly of the C1–C7 acyclic domain, and 3) a Nozaki–Hiyama–Kishi reaction for the construction of the C21–C28 side chain domain. The NMR spectroscopic discrepancies observed between synthetic 2 and the authentic sample as well as careful inspection of the Faulkner’s stereochemical assignment led us to postulate that the absolute configuration of the C10–C20 domain of 2 has been erroneously assigned. Accordingly, the total synthesis of the revised structure 65 was achieved to show that the NMR spectroscopic properties of synthetic 65 were in good agreement with those of the authentic sample. Furthermore, application of the phenylglycine methyl ester (PGME) method to the C7–C21 spiroacetal domain enabled us to establish the absolute configuration of didemnaketal B.     

Asymmetric Synthesis of the C（17）——C（28） Subunit of Didemnaketal B

The stereocontrolled synthesis of the C（17）--C（28） fragment 3 of didemnaketal B was accomplished in 21 steps from the natural （R）-（＋）-pulegone and （S）-（--）-citronellal. The key steps involved diastereoselective construction of two chiral carbon centers through the intramolecular chiral induction and uncommon Julia olefination of ketone forming the E-trisubstituted C（22）--C（23） double bound.     

Synthetic studies on taxol: highly stereoselective construction of the taxol C-ring via SN2' reduction of an allylic phosphonium salt

[reaction: see text] The highly stereoselective construction of the C3 stereogenic center of the taxol C-ring is described. The trans isomer at the C3-C8 position of the taxol C-ring, which is required for the total synthesis, as well as its diastereomeric cis isomer were successfully synthesized with highly diastereoselective S(N)2' reduction of the allylic phosphonium salts.     

Efficient regioselective protection of myo-inositol via facile protecting group migration

A cis-1,2-cyclohexanediol, 1,4,5,6-tetra-O-benzyl-myo-inositol, was selectively protected at the axial C2-hydroxyl via acid-mediated rearrangement of the corresponding 1,2-orthoacetate, or via the base-induced migration of a protecting group that had previously been easily installed with complete regioselectivity at the adjacent equatorial hydroxyl. Esters 4a-6a were synthesized in high yields (75-82%) while sulfonate 7a and silyl ether 8a were obtained in 85 and 31% yields, respectively. The migration of the esters induced by DBU results in equilibrium between regioisomers favouring the C2 protected isomer, but NaH induced migration of sulfonyl and silyl groups results in complete migration from equatorial to axial hydroxyl groups.     

Flame retardant polycyanurate thermosets from the cyanate esters of triphenylphosphine oxide

Three cyanate esters containing phosphorus are synthesized in good overall yields starting from bromoanisoles. Di‐ and tricyanates with meta configuration are most stable while para is less so. The para dicyanate ester isomer is particularly affected by water from the atmosphere. The meta dicyanate ester 2 has good thermal properties with glass transition at 268 °C and char yield of 65% in air at 600 °C. All three phosphorus‐containing cyanate esters are low flammability in an open flame. They make highly combustible cyanate esters resins less flammable simply by blending. Mixing 10 wt% dicyanate ester 2 into bisphenol A or E dicyanate esters makes them rate V‐0. Published 2018.^† J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1100–1110     

Use of the electrophilic c-arylation by aryllead triacetates in the construction of synthons for aizoaceae and amaryllidaceae alkaloid synthesis

The vinylogous β-keto esters, ethyl 2-methyl-4-oxocyclohex-2-ene-carboxylate (Hagemann's Ester) (4), ethyl 4-oxocyclohex-1-ene-carboxylate (7a) and its double bond isomer (7b), undergo regiospecific arylation with aryllead triacetates at C1; reaction of the mixture of isomers (7a) and (7b) with aryllead compounds (5a), (5c) and (5d) provides intermediates for the synthesis of (±)-o-methyl-joubertiamine (1), (±)-mesembrine (2) and (±)?lycoramine (3) respectively.     

Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement

A short formal total synthesis of the marine natural product diazonamide A is described. The route is based on indole oxidative rearrangement, and a number of options were investigated involving migration of tyrosine or oxazole fragments upon oxidation of open chain or macrocyclic precursors. The final route proceeds from 7‐bromoindole by sequential palladium‐catalysed couplings of an oxazole fragment at C‐2, followed by a tyrosine fragment at C‐3. With the key 2,3‐disubstituted indole readily in hand, formation of a macrocyclic lactam set the stage for the crucial oxidative rearrangement to a 3,3‐disubstituted oxindole. Notwithstanding the concomitant formation of the unwanted indoxyl isomer, the synthesis successfully delivered, after deprotection, the key oxindole intermediate, thereby completing a formal total synthesis of diazonamide A.     

Regio‐ and Stereochemical Studies on the Nitroso‐Diels–Alder Reaction with 1,2‐Disubstituted Dienes

The regioselectivity of the nitroso‐Diels–Alder reaction between unsymmetrical acyclic dienes and Boc‐nitroso (Boc=tert‐butoxycarbonyl) reagent or the Wightman chiral chloronitroso reagents has been studied. With the Boc‐nitroso reagent, the selectivity is a consequence of steric effects at the C1‐position in the diene and electronic effects at the C2‐position in the diene. The combination of an unprotected hydroxyethyl side chain at C1 and an electron‐withdrawing group at C2 allows complete regioselectivity in favour of the proximal isomer. The same isomer was obtained exclusively with the chiral nitroso reagent with high enantioselectivities. A model based on steric effects is proposed.     

Nonacid nitration of benzenedicarboxylic and naphthalenecarboxylic acid esters

When treated with nitrogen dioxide in the presence of ozone and a catalytic amount of iron(III) chloride in inert organic solvent at -10 to +5 degrees C, benzenedicarboxylic acid diesters 1, 4, and 6 underwent smooth nitration to give the corresponding mononitro derivatives 2/3, 5, and 7, respectively, in good yield (kyodai nitration). Naphthalenecarboxylic acid esters 8 and 11 and naphthalene-1,8-dicarboxylic acid diester 16 were similarly nitrated in the absence of catalyst to give the expected nitro compounds 9/10, 12-15, and 17-22, respectively. Different from conventional nitration based on the combined use of concentrated nitric and sulfuric acids, no hydrolytic cleavage of the ester function was observed under these conditions. The isomer distribution has been determined for the nitration of naphthalenecarboxylic acid esters 8, 11, and 16, and spectral data were collected for less common nitro derivatives. A unique changeover of the orientation mode observed in the kyodai nitration of diester 16, from the initial exclusive meta to the final meta/para, has been discussed in terms of the competition between the electrophilic substitution process involving the nitronium ion (NO2+) and the addition-elimination sequence involving the nitrogen trioxide radical (*NO3).     

Synthesis and biological studies of some new acrylic acid ethyl esters of quinolinone

Abstract  

A series of new acrylic acid ethyl esters of quinolinones were synthesized from 4-(bromomethyl)quinolinones and screened for in vitro antimicrobial and in vivo analgesic and anti-inflammatory activities. Most of the compounds with chloro substitution at the C-6 or C-7 position in the quinolinone moiety and a methoxy group in the aryloxy moiety showed potent antibacterial and antifungal activities when compared with non-halogenated quinolinones and the quinolinones bearing a CH₃ at the C-8 position. In a pharmacological evaluation, the halogen substitution at the C-6 or C-7 position in quinolinones was found to enhance both analgesic and anti-inflammatory activities of the molecule when compared with a simple unsubstituted (non-halogenated) quinolinone. The structures of all newly synthesized compounds were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR, and FAB-MS.     

On the synthesis of pyrinodemin A. Part 1: The location of the olefin

The elucidation of the structure of the cytotoxic marine sponge alkaloid pyrinodemin A by synthesis is described. Based on the ¹³C NMR spectra of three double bond positional isomers and the natural product, it is concluded the C14′-C15′ isomer best represents the true structure of pyrinodemin A. In addition, the structural assignment of pyrinodemin C is evaluated.     

Computational mechanistic study of PMe3 and N-heterocyclic carbene catalyzed intramolecular Morita-Baylis-Hillman-like cycloalkylations: the origins of the different reactivity

It has been experimentally reported that PMe(3) catalyzes the cycloalkylation of the pendant halogenated α,β-unsaturated ketones (e.g., 1) at the C(α) position, whereas NHC catalyzes the cycloalkylation of the pendant halogenated α,β-unsaturated esters (e.g., 2) at the C(β) position. A DFT study has been performed to understand the detailed reaction mechanisms and the causes for the different ring closure positions in the two cycloalkylations promoted by the similar catalysts. Both reactions undergo three stages that include the nucleophilic addition of the catalysts (PMe(3) or NHC) to the substrates (1 or 2) and subsequent ring closure via S(N)2 mechanism, the H-elimination by the bases (KOH or K(3)PO(4)), and the catalyst release giving the final products. The first stage in the NHC-catalyzed reaction involves a favorable H-transfer step leading to the umpolung Michael acceptor, which is more stable than the nucleophilic addition complex. The H-transfer turns off the possibility to close ring at C(α) position for the reaction. In contrast, the similar H-transfer in the PMe(3)-catalyzed reaction is thermodynamically unfavorable. According to the electronic structure of the addition complex of PMe(3) to substrate (1), we rationalize why the experimentally isolated intermediate in the PMe(3)-catalyzed reaction is the trans-cyclic ketophosphonium salt, rather than its cis isomer that favors electrostatic attraction. The differences and the similarities among the two reactions and the traditional MBH reaction are discussed.     

A new method for the identification and the structural characterisation of carotenoid esters in freshwater microorganisms by liquid chromatography/electrospray ionisation tandem mass spectrometry

Liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS) has been employed to identify carotenoid esters present in raw organic extracts of pigmented freshwater microalgae and to gain structural information on these compounds. In particular, acyl carotenoid derivatives of Haematococcus pluvialis and Euglena sanguinea have been characterised by tandem mass spectrometry (MS/MS) in a quadrupole ion trap. ESI-MS/MS allows recognition of the presence of carotenoid esters in complicated mixtures without any initial chromatographic work-up and without the need to use UV-Vis photo-diode array (PDA) detectors. Product ion scans of the [M + Na]+ ion lead to known neutral losses of the C7H8 and C8H10 residues from the conjugated polyene moiety of the carotenoid unit, that permit the unambiguous identification of the carotenoid itself. These structurally relevant ions are not observed in positive or negative ion APCI (atmospheric pressure chemical ionisation) mass spectra. Moreover, the several product ions observed in positive and/or negative ion ESI-MS/MS not only are a diagnostic signature of the main structural features of the acyl chains such as length, position and unsaturation, but also display the nominal mass of the parent xanthophyll. Our methodology has been validated (i) by using esters of astaxanthin obtained from off-line purification of the H. pluvialis extracts and structurally elucidated through proton nuclear magnetic resonance (1H-NMR) spectroscopy and (ii) by product analysis of esters by alkaline hydrolysis. The characterisation of the unknown carotenoid esters of E. sanguinea is a demonstration of the capabilities of this methodology.     

A biomimetic cascade for the formation of the methyl [2(5H)-furanylidene]ethanoate core of spongosoritin A and the gracilioethers

The polyketide secondary metabolites spongosoritin A and gracilioethers A–C contain a unique methyl [2(5H)-furanylidene]ethanoate core. A synthetic model of a suspected biosynthetic intermediate to these natural products was constructed in seven steps and 48% overall yield. This model undergoes a facile cyclisation/double dehydration cascade to give the desired furanylidene motif, with the required (2Z) isomer obtained in >90 dr when an ethyl substituent is located at C3′ of the furanylidene.     

Nitration of 7- and 8-methyl-4-R-1H-2, 3-dihydro-1,5-benzodiazepin-2-ones

4-R-8-Methyl-2,3-dihydro-1H-1,5-benzodiazepin-2-ones are nitrated in the 7 position, whereas their 7-methyl analogs are nitrated in the 1, 8, or 9 position. The nitration of 4,8-dimethyldihydrobenzodiazepinone proceeds as primary substitution at the N₁ atom of the amide group. The resulting N₁-nitroamide undergoes prototropic rearrangement to the 9-nitro isomer in strongly acidic media.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 122–126, January, 1978.