Allenes in catalytic asymmetric synthesis and natural product syntheses

Allenes are the simplest class of cumulenes, with two contiguous C=C bonds, and show unique physical and chemical properties. These features make allenes particularly attractive in modern organic chemistry. In this Review, attention is paid to the advances made in catalytic asymmetric synthesis and natural product syntheses based on well-established reactions of allenes, such as propargylation, addition, cycloaddition, cycloisomerization, cyclization, etc., with or without catalysts. Their versatile reactivity, substituent-loading ability, axial to center chirality transfer, and controllable selectivity allow access to target molecules by unique and efficient approaches. The main topics in this Review are presented with selected examples from 2003 to 2011.     

Arynes and cyclohexyne in natural product synthesis

This Minireview highlights recent advances in the field of aryne and cyclohexyne chemistry that have allowed the extraordinary reactivity of these entities to be harnessed during the course of natural product syntheses. The syntheses presented rely on the use of these reactive species in chemoselective transformations and follow unprecedented synthetic strategies that are inspiring for the practitioners of synthetic organic chemistry.     

Total synthesis of the cytostatic marine natural product dibromophakellstatin via three-component imidazolidinone anellation

The tetracyclic pyrrole-imidazole alkaloid dibromophakellstatin from the marine sponge Phakellia mauritiana has been synthesized within seven steps from pyrrole in an 18% overall yield. The key step is a three-component assembly of a tricyclic enamide, a nitrene, and a carbamoyl building block, affording the imidazolidinone ring of dibromophakellstatin in one step. Notably, it is possible to employ the reagent EtO2CNHOTs in a double function as a source of the electrophilic nitrene and of a dipolar carbamoyl component. Use of debrominated precursor dipyrrolopyrazinones leads to much higher anellation yields and allowed us to develop a second generation synthesis. The cytostatic activity of dibromophakellstatin is confirmed.     

ortho-Quinone methides in natural product synthesis

ortho-Quinone methides (o-QMs) are emerging as highly useful intermediates, the inherent reactivity of which can be used in linchpin reactions for the construction of complex natural products. This review encompasses the major contributions in this field, exemplifying the major strategies and reactivity modes which can be applied.     

Cascade polycyclisations in natural product synthesis

The efficient, stereocontrolled construction of polycyclic ring systems has long presented a formidable challenge to synthetic chemists. Cascade reactions offer a 'quick fix'--building multiple rings in a single step--and often dramatically shorten a synthetic route. In this Emerging Area article, a selection of the most recent and impressive examples of applications of this tactic to natural product synthesis are discussed, which demonstrate the ambition and achievements of the modern synthetic chemist.     

Peptides that anneal to natural collagen in vitro and ex vivo

Collagen comprises ? of the protein in humans and ? of the dry weight of human skin. Here, we implement recent discoveries about the structure and stability of the collagen triple helix to design new chemical modalities that anchor to natural collagen. The key components are collagen mimetic peptides (CMPs) that are incapable of self-assembly into homotrimeric triple helices, but are able to anneal spontaneously to natural collagen. We show that such CMPs containing 4-fluoroproline residues, in particular, bind tightly to mammalian collagen in vitro and to a mouse wound ex vivo. These synthetic peptides, coupled to dyes or growth factors, could herald a new era in assessing or treating wounds.     

Recent advances in biomimetic natural product synthesis

This review highlights some of the most elegant and instructive biomimetic syntheses of natural products over the last few years, providing an updated overview of this area of research.     

Divergent strategy in natural product total synthesis

Divergent strategy in natural product synthesis allows the comprehensive synthesis of family natural products. Efficient formulation of this idea requires the biosynthetic/biosynthesis-inspired insight toward the well-orchestrated design of a pluripotent late-stage intermediate, in concomitant with the applicability of the intermediates for versatile transformations. This digest focuses on the actual applications of those strategies in natural product synthesis with an emphasis on the recipes for the choice of the common intermediates.     

The tethered Biginelli condensation in natural product synthesis

This review describes the development of the tethered Biginelli condensation and its application to the total synthesis of structurally complex, bioactive guanidine alkaloids.     

The Kulinkovich hydroxycyclopropanation reaction in natural product synthesis

The Kulinkovich cyclopropanation reaction provides a flexible and convenient method for the synthesis of cyclopropanols. Together with the diverse chemistry of the cyclopropanol unit, it offers access to a wide range of functionalised unsaturated and saturated compounds. The successful use in the synthesis of natural compounds is outlined in this perspective.     

环戊二烯及其衍生物在天然产物合成中的应用

报导了用环戊二烯作原料合成了(iridoids)和9-异氰(9-isocyanopupukeanane)的路线。     

The first total synthesis of the natural product angoluvarin

The total synthesis of angoluvarin, a member of the dihydrochalcone family of natural products, is reported. Starting with 2-bromophenol, the synthesis was accomplished in eight steps with an overall yield of 2%. This represents the first reported synthesis of angoluvarin.     

Total synthesis of the anticancer natural product OSW-1

The highly potent anticancer natural saponin OSW-1 has been successfully synthesized from commercially available 5-androsten-3beta-ol-17-one 79 in 10 operations with 28% overall yield. The key steps in the total synthesis included a highly regio- and stereoselective selenium dioxide-mediated allylic oxidation of 80 and a highly stereoselective 1,4-addition of alpha-alkoxy vinyl cuprates 68 to steroid 17(20)-en-16-one 12E to introduce the steroid side chain. This total synthesis demonstrated once again the versatile synthetic applications of alpha-halo vinyl ether chemistry developed in our laboratories.     

Novel total synthesis of the anticancer natural product dysidiolide

The marine natural product dysidiolide has been synthesized in a highly diastereoselective fashion that features the sequential transfer of chirality from a cyclohexenone precursor.     

Total synthesis of epoxyquinone meroterpenoid natural product biscognienyne B

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