Synthesis of hybrids between the alkaloids rutaecarpine and luotonins A, B

The synthesis of 7,12-dihydroindolo[2′,3′:3,4]pyrrolo[2,1-b]quinazolin-5-one, a hybrid compound containing common structural features of the natural alkaloids rutaecarpine (Evodia rutaecarpa) and luotonin A (Peganum nigellastrum), was performed by active methylene group transformations of deoxyvasicinone. The synthesis of 7-hydroxy-8-norrutaecarpine was accomplished via the first total synthesis of bouchardatine (Bouchardatia neurococca) and its acid-catalyzed ring closure. The synthesized alkaloid analogues are the first representatives of a new heterocyclic ring system. Preliminary testing of the synthesized compounds showed cytotoxic activities against HeLa cells and apoptosis inducing effects at a concentration comparable to that of the control drug, etoposide.     

A facile total synthesis of rutaecarpine

The indoloquinazoline alkaloid rutaecarpine has been synthesized efficiently by employing 9,10,11,12-tetrahydro-4H-pyrido[2,1-b]quinazoline-4,9-dione (4) as a key intermediate, which was prepared by adapting a Dieckmann condensation-decarboxylation sequence from quinazolinone diester 6.     

A Concise Total Synthesis of S-（＋）-Tylophorine

A highly efficient total synthesis of S-( )-tylophorine has been accomplished in fully asymmetric fashion.     

A Concise Synthesis of (－)-Indolizidines 209D and 209B

A general stereoselective synthetic route to 5-substituted and 5,8-disubstituted indolizidine alkaloids has been developed starting from commercially available L-proline. (－)-Indolizidines 209D and 209B were efficiently synthesized in 9.8% and 14.8% overall yields in seven and five-step reactions from readily available aldehyde 3 and ketone 10, respectively. The key steps of this synthesis involve a substrate-induced asymmetric addition of ethyl lithiopropiolate to aldehyde 3 or methyl ketone 10, and a two-step one-pot hydrogenation/cyclization sequence to construct the bicyclic skeleton.     

靶向抑制DNA拓扑异构酶的抗肿瘤药物研究

DNA拓扑异构酶是真核细胞和原核细胞中的一种基本酶,广泛存在于细胞核中,对DNA的转录、复制以及基因表达过程中的DNA拓扑结构的改变起着重要的作用。研究发现DNA拓扑异构酶在肿瘤组织中高度表达,许多抗肿瘤药物的作用机制与抑制拓扑异构酶有关,目前拓扑异构酶已成为筛选抗肿瘤药物的重要靶点。     

Concise total synthesis of AB5046A and AB5046B

Two naturally occurring rare 5-oxo β-triketones, AB5046A and AB5046B, were efficiently synthesized in five linear steps with overall yields of 36% and 28%, respectively. The synthetic strategy highlighted the readily preparation of the key intermediate, 3-ethoxy-5-hydroxycyclohex-2-enone, from commercially available phloroglucinol.     

Phormidinines A and B, novel 2-alkylpyridine alkaloids from the cyanobacterium Phormidium sp.

Novel 2-alkylpyridine alkaloids, phormidinines A (1) and B (2), were isolated from cyanobacterium Phormidium sp. Their structures were determined by spectroscopic analysis. The absolute stereochemistry of 1 was established by the modified Mosher’s method.     

Expedious and practical synthesis of the bioactive alkaloids rutaecarpine, euxylophoricine A, deoxyvasicinone and their heterocyclic homologues

Efficient assembly of pyrimido-β-carbolines 1 and 2, including the bioactive alkaloids rutaecarpine, euxylophoricine A, and deoxyvasicinone (3), is reported from suitable aromatic amino acids 7 or corresponding aromatic amino esters 8 and imino-thioethers 5 or 6 in a one-step sequence in moderate to good yields. The key step of this methodology is based on an intramolecular aza-displacement of a methylthio group followed by spontaneous cyclodehydration. Furthermore, when aromatic amino esters 8 were used instead of amino acids, a tandem amino-methylthio displacement/amino ester cyclization takes place.     

Bistabercarpamines A and B,first vobasinyl-chippiine-type bisindole alkaloid from Tabernaemontana corymbosa

Two novel dimeric monoterpene indole alkaloids, bistabercarpamines A (1) and B (2) possessing unprecedented bis-vobasinyl-chippiine-type skeleton, were isolated from the leaves of Tabernaemontana corymbosa. The structures were elucidated on the basis of spectroscopic data, and the absolute configurations of these isolates were determined by CD excition chirality method. Bistabercarpamine A (1) exhibited moderate cell growth inhibitory activity against HepG-2 cells with IC₅₀ of 38.14 ± 1.1 μM.     

Concise total synthesis of phidianidine A and B

The shortest total synthesis of cytotoxic indole alkaloids phidianidine A and B is described. Rapid assembly of the 1,2,4-oxadiazole core from a novel N-hydroxyguanidine and the corresponding indole-3-acetic acid chloride led to formal syntheses of phidianidine A and B in only three steps from known compounds. Deprotection under standard conditions provided the trifluoroacetate salts of phidianidine A and B in quantitative yield.     

Concise total synthesis of calothrixins A and B

The concise total synthesis of calothrixins A and B has been accomplished by utilizing the one-pot formation of hexatriene as a key intermediate via the palladium-catalyzed tandem cyclization/cross-coupling reaction of triethyl(indol-2-yl)borate. In another key transformation, the indolo[3,2-j]phenanthridine core was prepared in high yield via Cu(I)-mediated 6π-electrocyclization.     

Concise, asymmetric, stereocontrolled total synthesis of stephacidins A, B and notoamide B

Concise asymmetric total syntheses of the fungal metabolites (-)-stephacidin A, (+)-stephacidin B, and (+)-notoamide B are described. Key features of these total syntheses include (1) a facile synthesis of (R)-allyl proline methyl ester, (2) a revised route toward the pyranoindole ring system, (3) a novel cross-metathesis strategy for the introduction of important functional groups, and (4) an SN2' cyclization to form the [2.2.2] bridged bicyclic ring system. Furthermore, our synthesis has taken advantage of microwave heating to shorten reaction times as well as increase yields for the preparation of vital intermediates.     

One-pot reductive-cyclization as key step for the synthesis of rutaecarpine alkaloids

The quinazolinocarboline alkaloids including rutaecarpine (1a), euxylophoricine A (1b), and euxylophoricine C (1c) have been synthesized efficiently from the ring opened β-carboline derivative as key intermediate by a one-pot reductive-cyclization reaction. The key intermediate was prepared from tryptamine (6) following Bischler-Napieralski cyclization, benzoylation, and oxidative cleavage of the exocyclic double bond.     

Total synthesis of the cytotoxic alkaloid 22-hydroxyacuminatine

The total synthesis of the cytotoxic alkaloid 22-hydroxyacuminatine has been achieved in 14.9% overall yield starting from 2-methylcinnamic acid via the key intermediate 5-ethoxymethylisoquinolin-1-one.     

Total synthesis of cytotoxic sponge alkaloids hachijodines F and G

The total synthesis of two cytotoxic sponge alkaloids hachijodines F and G has been achieved. The synthesis of both compounds utilises a common intermediate alkyne. By comparison of spectra the structure of the natural product has been confirmed.     

Concise total synthesis and stereochemical revision of (+)-naseseazines A and B: regioselective arylative dimerization of diketopiperazine alkaloids

Concise and enantioselective total syntheses of (+)-naseseazines A and B are described. Our regioselective and directed dimerization of diketopiperazines provides their critical C3-C(sp(2)) linkages, an assembly with plausible biogenetic relevance. We revise the absolute stereochemistry of (+)-naseseazines A and B.     

Concise synthesis of pyrrolophenanthridine alkaloids using a Pd-mediated biaryl coupling reaction with regioselective C-H activation via the intramolecular coordination of the amine to Pd

The concise synthesis of Amaryllidaceae alkaloids, such as anhydrolycorinone, anhydrolycorin-7-one, assoanine, and oxoassoanine, which have a pyrrolophenanthridine skeleton, was achieved in moderate yield using the Pd-mediated biaryl coupling reaction of 1-(2-halobenzyl)-2,3-dihydroindole, which applied the regioselective C-H activation method with intramolecular coordination of the benzylamino group to Pd.     

Aconapelsulfonines A and B,seco C20-diterpenoid alkaloids deriving via Criegee rearrangements of napelline skeleton from Aconitum carmichaelii

Two sulfo nated seco C₂₀-diterpenoid alkaloids,aconapelsulfonines A(1) and B(2),were isolated from an aqueous extract of the raw material of "Fu Zi"(the Aconitum carmichaelii lateral roots),of which the structures were elucidated by various spectroscopic data,combined with X-ray crystallogra phic analysis.The unprecedented skeletons are biogenetically proposed to be derived via Criegee rearrangements of the napelline-type architecture.The two compounds exhibited dose-depended analgesic activities on an acetic acid-induced mice writhing test.     

Antiviral activity of aconite alkaloids from Aconitum carmichaelii Debx

Four diterpenoid alkaloids, namely, (a) hypaconitine, (b) songorine, (c) mesaconitine and (d) aconitine, were isolated from the ethanol root extract of Aconitum carmichaelii Debx. The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were evaluated. Antiviral activity test in vivo showed that compounds a and c, which were C19-diterpenoid alkaloids, showed inactivation efficacy values of 82.4 and 85.6% against TMV at 500 μg/mL, respectively. By contrast, compound c presented inactivation activity of 52.1% against CMV at 500 μg/mL, which was almost equal to that of the commercial Ningnanmycin (87.1% inactivation activity against TMV and 53.8% inactivation activity against CMV). C19-Diterpenoid alkaloids displayed moderate to high antiviral activity against TMV and CMV at 500 μg/mL, dosage plays an important role in antiviral activities. This paper is the first report on the evolution of aconite diterpenoid alkaloids for antiviral activity against CMV.     

Concise and efficient synthesis of calothrixin B

A convergent synthesis of the naturally occurring alkaloid Calothrixin B is presented, which used a regioselective hetero-Diels-Alder reaction between a "push-pull" 2-aza-diene and a N-protected 3-bromo-9H-carbazole-1,4-dione to construct the five-ring skeleton of the molecule. Protection of the indole motif with a benzyl group was unattractive for delivery of sufficient target material because the removal of the protecting group had not been high yielding. We therefore elected to temporarily protect the indole motif with a more labile benzyloxycarbonyl group. Accordingly, the synthesis of calothrixin B proceeded in 17% overall yield over 9 steps from the commercially available 1,2,3,9-tetrahydro-4H-carbazol-4-one.