Enantioselective biomimetic total syntheses of katsumadain and katsumadain C

Enantioselective total syntheses of katsumadain and katsumadain C were achieved concisely through a biomimetic approach. Assembly of styryl-2-pyranone (3) and monoterpene 6 via acid-promoted regio- and stereoselective C-C bond formation afforded katsumadain (2), which underwent the photoinduced [2 + 2] dimerization in a head-to-tail mode to furnish katsumadain C (1).     

Studies on the resorcylates: biomimetic total syntheses of (+)-montagnetol and (+)-erythrin

6-(2,4-Dioxopentyl)-2,2-trimethyl-4H-1,3-dioxin-4-one on reflux in toluene gave MeCOCH₂COCH₂COCHCO, which cyclized to 6-(2-oxopropyl)-4-hydroxy-2H-pyran-2-one or was trapped with alcohols to produce resorcylate esters. The method was used for the synthesis of both enantiomers of montagnetol and erythrin.     

Efficient total syntheses of natural pterin glycosides: limipterin and tepidopterin

The key, versatile precursors N²-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (29a) and its ciliapterin analog (29b) were prepared, respectively, from d-xylose (in 14 steps) and l-xylose (in 11 steps). Treatment of 29a and 29b with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl bromide in the presence of silver triflate and tetramethylurea, followed by removal of the protecting groups, led to the first selective syntheses of limipterin (3) and tepidopterin (5), respectively.     

Short total syntheses of the avenaciolide family of natural products

The avenaciolide family of natural products are small α-methylene bis-γ-lactones that exhibit a wide variety of biological activities. Herein we report concise syntheses of five members of this family of natural products along with the synthesis of one non-natural analogue. The syntheses proceed in five or six steps from simple, commercially available compounds and feature a key oxidative cyclization/lactonization reaction that likely occurs via a radical mechanism.     

Recent topics in total syntheses of natural dimeric naphthoquinone derivatives

This digest overviews successful synthetic approaches to natural dimeric 1,4-naphthoquinones. Several natural dimeric 1,4-naphthoquinone derivatives have been isolated from natural sources including plants, bacteria, and fungi. They have diverse structures and attractive biological activities. However, it is difficult to construct the dimeric scaffolds efficiently and selectively, because 1,4-naphthoquinones and their derivatives are highly reactive. Efficient and attractive synthetic methodologies to construct unique dimeric 1,4-naphthoquinone skeletons are reviewed.     

Evolution of the total syntheses of ustiloxin natural products and their analogues

Ustiloxins A-F are antimitotic heterodetic cyclopeptides containing a 13-membered cyclic core structure with a synthetically challenging chiral tertiary alkyl-aryl ether linkage. The first total synthesis of ustiloxin D was achieved in 31 linear steps using an S(N)Ar reaction. An NOE study of this synthetic product showed that ustiloxin D existed as a single atropisomer. Subsequently, highly concise and convergent syntheses of ustiloxins D and F were developed by utilizing a newly discovered ethynyl aziridine ring-opening reaction in a longest linear sequence of 15 steps. The approach was further optimized to achieve a better macrolactamization strategy. Ustiloxins D, F, and eight analogues (14-MeO-ustiloxin D, four analogues with different amino acid residues at the C-6 position, and three (9R,10S)-epi-ustiloxin analogues) were prepared via the second-generation route. Evaluation of these compounds as inhibitors of tubulin polymerization demonstrated that variation at the C-6 position is tolerated to a certain extent. In contrast, the S configuration of the C-9 methylamino group and a free phenolic hydroxyl group are essential for inhibition of tubulin polymerization.     

Facile biomimetic syntheses of the azaspiracid spiroaminal

The azaspiracid natural products display a common spiroaminal-containing terminal domain that has inspired the development of two new methods for spiroaminal syntheses—a Staudinger reduction-aza-Wittig process and a double intramolecular hetero-Michael addition. These effective laboratory approaches proceed through imine and enamine intermediates that may reflect transient biogenetic species.     

Expeditious total syntheses of natural allenic products via aromatic ring umpolung

Concise diastereoselective syntheses of the marine (+/-)-panacene and terrestrial (+/-)-desbromopanacene have been achieved in a few steps based on a concept of "aromatic ring umpolung". The synthetic avenue to the (+/-)-panacene involved a novel oxymercuration strategy to produce the correct configuration of the bromoallene moiety.     

The power of singlet oxygen chemistry in biomimetic syntheses

Herein, we describe selected highlights from the successful syntheses of the litseaverticillol family of natural products and from the synthesis of the core of the prunolide molecules, using powerful ¹O₂-orchestrated biomimetic strategies. In these syntheses, cascade reaction sequences initiated by the reaction of ¹O₂ with a furan and the ene-reaction of ¹O₂ with double bonds together facilitated the swift assembly of the targeted compounds from simple precursors. We also introduce our most recent ¹O₂-facilitated synthetic strategies used in our approach to the synthesis of premnalane A. In this investigation, we explore a number of different reactivities of ¹O₂, thus completing a brief survey of how ¹O₂ chemistry may be fruitfully employed in the synthesis of complex secondary metabolites.     

A comparative analysis of the total syntheses of the amphidinolide T natural products

In this article we compare and contrast the strategies and tactics used in the syntheses of the amphidinolide T family of natural products that have been reported by Fürstner, Ghosh and ourselves. Similar approaches to the trisubstituted THF ring present in the targets are utilized in all of the syntheses, but each strategy showcases a different means of macrocyclization.     

芳香杂环并吡咯的合成和在天然产物全合成中的应用

叠氮基-丙二酸烷叉酯的分子内1,3-二极环加成和环翻转反应被用于制备异缩合杂环芳香吡咯的新方法, 报导了这一方法用于合成2,4-二氢吡咯[3,4-b]吲哚环系, 同样这一环系被用于椭园玫瑰树碱的全合成。     

Pericyclic reactions of prenylated naphthoquinones: biomimetic syntheses of mollugin and microphyllaquinone

[reaction: see text] A total synthesis of the bioactive naphthohydroquinone mollugin and the related naphthoquinone dimer microphyllaquinone is described. Both syntheses exploit the propensity of prenylated quinones to undergo tautomerization/oxa 6pi-electrocyclizations.     

Enantioselective total syntheses of (+)-decursin and related natural compounds using catalytic asymmetric epoxidation of an enone

The enantioselective total syntheses of (+)-decursin (1) and related natural dihydropyranocoumarins (−)-prantschimgin (3), (+)-decursinol (4), and (+)-marmesin (5) were achieved for the first time using catalytic asymmetric epoxidation of an enone as the key step. Catalytic asymmetric epoxidation of the enone was effectively promoted by the novel multifunctional asymmetric catalyst generated from La(O-i-Pr)₃, BINOL, and Ph₃AsO in a 1:1:1 ratio to afford epoxide in 94% yield and 96% ee, which was recrystallized to give optically pure epoxide. After conversion to the common key intermediate (−)-peucedanol (7), all natural dihydropyranocoumarins were synthesized through palladium-catalyzed intramolecular C-O coupling reactions. A possible reaction mechanism of the catalytic asymmetric epoxidation of enones is also described based on X-ray analysis, laser desorption/ionization time-of-flight mass spectrometry, kinetic studies, and asymmetric amplification studies.     

A biomimetic total synthesis of (+)-intricarene

An asymmetric synthesis of the furanocembrane (−)-bipinnatin J (3a) found in gorgonian corals is described. Treatment of 3a with VO(acac)₂-^tBuOOH, followed by acetylation, gave acetoxypyranone 15. When 15 was heated in the presence of DBU, it underwent a transannular oxidopyrylium-alkene [5+2] cycloaddition producing the polycyclic diterpene (+)-intricarene 1, isolated from the coral Pseudopterogorgia kallos. The total synthesis of intricarene 1 mimics its most likely biosynthesis via oxidation of bipinnatin J (3a) in vivo.     

Chemical syntheses of inulin and levan structures

A fructofuranosyl thiglycoside donor, ethyl 6-O-acetyl-3-O-benzyl-1,4-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-2-thio-beta-D-fructofuranoside (11), designed to yield stereospecifically beta-linkages and also to allow subsequent elongation in the 6- and/or 1-positions, was prepared and used in syntheses of levan and inulin structures. DMTST-promoted glycosylation between 11 (1.3 mol equiv) and methyl beta-D-fructofuranoside 6-OH and 1-OH acceptors (3 and 6) gave stereospecifically the protected methyl levanobioside 12 and inulinobioside 17 in excellent yields (80 and 86%), respectively. Protecting group manipulations on these afforded new disaccharide 6'-OH and 1'-OH acceptors (13 and 19), which were coupled again with donor 11 (1.0 mol equiv) to yield methyl levanotrioside 14 and inulinotrioside 20 in high yields, 65 and 67%, respectively. These were transformed into new acceptors and also fully deprotected to afford the methyl glycosides of levanotriose and inulinotriose, all structures that have earlier not been accessible by chemical synthesis.     

Practical total syntheses of epiquinamide enantiomers

Short and practical syntheses of epiquinamide and its enantiomer were accomplished with high overall yields and high stereoselectivity from readily available starting materials.