Synthetic studies on (+)-ophiobolin A: asymmetric synthesis of the spirocyclic CD-ring moiety

[reaction; see text] Asymmetric synthesis of the spirocyclic CD-ring moiety of (+)-ophiobolin A is described. Fragment A, which was prepared via pig liver esterase (PLE)-mediated kinetic resolution, and fragment B, which was prepared via diastereoselective allylation and subsequent kinetic iodolactonization, were coupled to afford the allylsilane 2, which was successfully cyclized to the desired spirocyclic CD-ring moiety 1a in the presence of a Lewis acid.     

Modular synthesis of 1-α- and 1-β-(indol-2-yl)-2'-deoxyribose C-nucleosides

A simple two-step method for the selective preparation of anomerically pure 1α- and 1β-(indol-2-yl)deoxyribose derivatives was developed. The synthesis was based on the Sonogashira reaction of 1α- and 1β-ethynyldeoxyribose and 2-haloanilines followed by a Pd-complex catalyzed cyclization to the corresponding indolyldeoxyribosides.     

Total synthesis of siphonarin B and dihydrosiphonarin B

The spirocyclic core of the siphonarins was constructed by a directed cyclization of a linear triketone, prepared using a Sn(II)-mediated aldol coupling and Swern oxidation at C9 and C13. To circumvent a facile retro-Claisen pathway generating a baconipyrone-type ester, a Ni(II)/ Cr(II)-mediated coupling reaction with vinyl iodide was used to complete the first synthesis of siphonarin B and dihydrosiphonarin B. A stable isomeric spiroacetal was also prepared which could not be equilibrated to the siphonarin skeleton.     

Total synthesis of chaetominine

An efficient, asymmetric synthesis of the cytotoxic natural product chaetominine was achieved in 14 steps. The strategy employs a copper(I)-mediated cyclization reaction as a key step to install the abc-tricyclic ring system, which was further elaborated by diastereoselective oxidation and reduction reactions. This effort also documents the first example of an oxidative rearrangement yielding to homochiral spirocyclic pyrrolidinyloxindoles.     

Samarium(II)-mediated spirocyclization by intramolecular aryl radical addition onto an aromatic ring

Samarium(II)-mediated spirocyclization by intramolecular addition of aryl radicals onto an aromatic ring was achieved by the reaction of N-(2-iodophenyl)-N-alkylbenzamides with SmI2 in the presence of HMPA, yielding spirocyclic indolin-2-one derivatives. The ether congeners afford spirocyclic benzofuran derivatives in moderate yields by aryl radical addition onto a benzene ring without having an electron-withdrawing group. The reaction with other aryl groups such as naphthalene and indole rings is also described.     

Asymmetric Addition of Diethylzinc to Aldehydes Using SPINOL Derivatives

Lewis acid catalyzed enantioselective carbon-carbon bond formation is one of the most interesting challenges in catalytic asymmetric synthesis. A convenient route for this synthesis is the addition of organozinc to aldehydes.[1]1,1'-Spirobiindane-7,7'-diol (SPINOL), a new reported C2 symmetrical diol, was recently proven to be an excellent framework for chiral ligands.[2] In this paper, interestingly, we describe the preparation of SPINOL derivatives and application of these ligands to asymmetric addition of diethylzinc to aldehydes as model reaction. Previously, an improved method for the resolution of C2-symmetric spirocyclic SPINOL was presented with crude menthyl chloroformate as resolving reagent.[3] Then (R)-SPINOL with C2-symmetric spirocyclic framework was applied in the asymmetric diethylzinc addition to aromatic aldehydes, which induced high conversions and moderate enantioselectivities for the production of chiral secondary alcohols. Further work of other SPINOL derivative ligands for asymmetric diethylzinc addition to aromatic aldehydes and developing further new SPINOL-based Lewis acid catalyzed asymmetric synthesis are underway.     

Reliable Synthesis of Various Nucleoside Diphosphate Glycopyranoses

A reliable and high yielding synthetic pathway for the synthesis of the biologically highly important class of nucleoside diphosphate sugars (NDP‐sugars) was developed by using various cycloSal‐nucleotides 1 and 9 as active ester building blocks. The reaction with anomerically pure pyranosyl‐1‐phosphates 2 led to the target NDP‐sugars 20 – 45 in a nucleophilic displacement reaction, which cleaves the cycloSal moiety in anomerically pure forms. As nucleosides cytidine, uridine, thymidine, adenosine, 2′‐deoxy‐guanosine and 2′,3′‐dideoxy‐2′,3′‐didehydrothymidine were used while the phosphates of D ‐glucose, D ‐galactose, D ‐mannose, D ‐NAc‐glucosamine, D ‐NAc‐galactosamine, D ‐fucose, L ‐fucose as well as 6‐deoxy‐D ‐gulose were introduced.     

新型硼氮磷一体化阻燃剂的合成

分别以硼酸、二乙醇胺、三氯氧磷和季戊四醇为原料,经酯化反应制得中间体二乙醇胺硼酸酯（DEAB, 1）和双季戊四醇二氯磷酸酯（SPDPC, 2）; 1与2经缩聚反应合成新型集磷、氮、硼于一体的阻燃剂聚季戊四醇双磷酸酯二磷酰氯螺环二乙醇胺硼酸酯（PPSPSDB, 3）,其结构经¹H NMR, ¹³C NMR和FT-IR表征。考察了溶剂、物料比γ［n(2)：n(1)］、反应温度和反应时间对3产率的影响,结果表明：在最佳反应条件（DMF为溶剂,γ=1 ：1.2, 于120 ℃反应2 h后,于190 ℃反应2 h）下,产率93.26%。热重分析表明：3的初始分解温度为240.5 ℃, 800 ℃时残炭率为44.45%。     

The first synthesis of the ABC-ring system of 'upenamide

The first synthetic route to the spirooxaquinolizidinone core (ABC core) of the macrocyclic marine alkaloid 'upenamide (1) has been developed. All five stereocenters were introduced with complete stereocontrol. The hydroxyl group at C-11 was introduced by a regio- and stereoselective SeO(2)-mediated allylic oxidation. The spirocyclic skeleton was formed by a stannous chloride induced deacetalization-bicyclization procedure. Further stereocenters were introduced by an enzymatic desymmetrization and by incorporation of an (S)-malic acid derived building block.     

An efficient synthesis of a spirocyclic oxindole analogue

An efficient, scaleable synthesis approach towards the spirocyclic oxindole analogue 1'-(tert-butoxycarbonyl)-2-oxospiro[indoline-3,4'-piperidine]-5-carboxylic acid (1) is described. The key steps are dianion alkylation and cyclization of ethyl 2- oxindoline-5-carboxylate (4) and demethylation of the resulting spirocyclic oxindole ethyl 1'-methyl-2-oxospiro[indoline-3,4'-piperidine]-5-carboxylate (5). The target compound was obtained in an overall yield of 35 % over eight steps without resorting to chromatographic purification.     

Microwave‐assisted One‐pot,Three‐component Regiospecific and Sterospecific Synthesis of Spiro Indanone Pyrrolidine/Piperidine Fused Nitrochromene Derivatives Through 1,3‐Dipolar Cycloaddition Reactions

A simple, straightforward, and versatile protocol for the synthesis of spiro indanone pyrrolidine/piperidine fused nitrochromene derivatives is described. The synthesis of a new series of spirocyclic molecules has been expediently accomplished via a one‐pot, three component 1,3‐dipolar cycloaddition reaction. 2‐Phenyl‐nitrochromene dipolarophiles were reacted with azomethine ylides, generated in situ by the condensation of dicarbonyl compound indane‐1,3‐dione and secondary amino acid (L‐proline/pipecolic acid), to produce the corresponding cycloadducts in good yields (85–90%) under classical as well as under microwave irradiation. The cycloaddition reaction was found to be highly regiospecific and diasterospecific. The regiochemical and sterochemical outcome of the cycloaddition reaction is ascertained by 2D NMR (COSY and NOESY) studies.     

Synthesis of dihydrobenzoxazine pyrrolidone spirocyclic compounds

A simple and efficient synthetic strategy for the preparation of dihydrobenzoxazine spirocyclic compounds was reported via the cycloaddition reaction of o-succinimide-substituted benzaldehyde with nitrobenzene. The reactions can be conducted under very mild reaction conditions (room temperature) using 10?mol% of Cs₂CO₃ as catalyst. A series of dihydrobenzoxazine pyrrolidone spirocyclic compounds were afforded in moderate to good yields. This strategy provides a new direction for the synthesis and study on biological activities of dihydrobenzoxazine pyrrolidone spirocyclic compounds.     

Reaction of dihydrolipoic acid with juglone and related naphthoquinones: unmasking of a spirocyclic 1,3-dithiane intermediate en route to naphtho[1,4]dithiepines

The reaction of dihydrolipoic acid (DHLA) with 5-hydroxy-1,4-naphthoquinone (juglone) gives rise to the novel naphtho[1,4]dithiepine derivatives through ring expansion of an unstable spirocyclic 1,3-dithiane intermediate, which was isolated and completely characterized. Reported herein is also the characterization of novel reaction products of DHLA with other naphthoquinones and the extension of the study to the spirocyclic adduct formed by reaction with a representative 2-substituted naphthoquinone.     

Total synthesis of (+)-papulacandin D

A total synthesis of (+)-papulacandin D has been achieved in 31 steps, in a 9.2% overall yield from commercially available materials. The synthetic strategy divided the molecule into two nearly equal sized subunits, the spirocyclic C-arylglycopyranoside and the polyunsaturated fatty acid side-chain. The C-arylglycopyranoside was prepared in 11 steps in a 30% overall yield from triacetoxyglucal. The fatty acid side-chain was also prepared in 11 steps in a 30% overall yield from geraniol. The key strategic transformations in the synthesis are: (1) a palladium-catalyzed, organosilanolate-based cross-coupling reaction of a dimethylglucal-silanol with an electron-rich and sterically hindered aromatic iodide and (2) a Lewis-base catalyzed, enantioselective allylation reaction of a dienal and allyltrichlorosilane. A critical element in the successful execution of the synthesis was the development of a suitable protecting group strategy that satisfied a number of stringent criteria.     

A highly diastereoselective synthesis of chroman derivatives bearing spirocyclic N,O-acetals skeleton via a one-pot tandem reaction

A tandem reaction for the synthesis of chroman framework via a one-pot reaction of phenol, paraformaldehyde, and 5-benzylimidazolidin-4-one mediated by p-nitrobenzoic acid is described. The chroman derivatives containing spirocyclic N,O-acetal skeleton can be obtained in moderate to good yields (up to 89%) with good to excellent diastereoselectivities (up to >20:1 dr).     

Molecular diversity via amino acid derived alpha-amino nitriles: synthesis of spirocyclic 2,6-dioxopiperazine derivatives

[reaction: see text] Chiral spirocyclic 2,6-dioxopiperazines were synthesized from amino acid derived alpha-quaternary alpha-amino nitriles via H(2)SO(4)-promoted cyano hydration, followed by base-mediated cyclization and N-alkylation. This methodology, requiring the previous preparation of the amino nitrile by a modified Strecker reaction, was applied to Phe, Trp, Pro, Asp, Glu, and Ser derivatives. In the case of the Trp-derived amino nitrile the major product of the treatment with H(2)SO(4) was not the expected carboxamide, but a new tetracyclic indoline derivative containing the novel heterocyclic system hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indole, as a result of a domino tautomerization. The treatment of this indoline derivative with refluxing 1 N HCl led to a Trp-derived 2,6-dioxopiperazine. The 2,6-dioxopiperazine ring opened under the reaction conditions of methyl ester saponification, giving N-(carboxyalkyl)amino acid derivatives. Therefore, the synthesis of 2,6-dioxopiperazines containing free carboxylic acids from the respective methyl esters required transesterification to benzyl esters, followed by hydrogenolysis.     

Stereoselective synthesis of spirocyclic oxindoles based on a one-pot Ullmann coupling/Claisen rearrangement and its application to the synthesis of a hexahydropyrrolo[2,3-b]indole alkaloid

An efficient and convenient approach to the synthesis of spirocyclic oxindoles from iodoindoles has been developed. The most striking feature of this approach is that the sequential intramolecular Ullmann coupling and Claisen rearrangement proceeds in a one-pot manner to afford 3-spiro-2-oxindoles in good yield with excellent diastereoselectivity. Application of this one-pot reaction to chiral non-racemic tertiary alcohol substrates resulted in complete chirality transfer to the spirocyclic quaternary carbon. Using this method, asymmetric total synthesis of (−)-debromoflustramine B was accomplished.     

具有岩兰烷基本结构的螺[4,5]癸多烯的合成

利用1,5-二甲基-6-亚甲基环己烯和2,4-二氧代戊酸甲酯的deMayo反应,经加成产物retro-benzilic acid重排,一步构成岩兰烷属螺环倍半萜类天然产物的基本碳架,通过对螺环上的多种官能团进行化学修饰,合成一系列螺[4,5]癸多烯化合物.所合成的新化合物的化学结构均经IR,1H NMR及元素分析予以证实.     

螺环倍半萜(±)-茅苍术醇和(±)-沉香螺醇的改进合成

以2,4-二氧代戊酸甲酯(1)和1,5-二甲基-6-亚甲基环己烯(2)为原料,通过[2+2]光环加成和retro-Benzilicacid重排,合成了具有螺[4,5]癸烷结构的岩兰烷基本碳架的化合物3.用锌粉选择还原五元环上碳碳双键得螺环二酮(4),对环外羰基实施保护并将环上酮基转化为亚甲基得到重要的合成前体6,经与甲基溴化镁的格氏反应生成混合的标题化合物.利用羟基和异氰酸苯酯的反应生成一对N-苯基氨基甲酸酯异构体(12),二者分离后经四氢铝锂还原,完成了螺环倍半萜(±)-茅苍术醇和(±)-沉香螺醇的全合成.     

A concise approach for the total synthesis of pseudolaric acid A

A new strategy for the stereoselective total synthesis of natural product pseudolaric acid A (1) was accomplished in 16 steps from commercially available starting material, featuring a samarium diiodide (SmI(2))-mediated intramolecular alkene-ketyl radical cyclization and a ring-closing metathesis (RCM) reaction to stereoselectively cast the unusual trans-fused [5-7]-bicyclic core of pseudolaric acid A (1).