Synthesis of optically pure 2,3,4-trisubstituted tetrahydrofurans via a two-step sequential Michael-Evans aldol cyclization strategy: total synthesis of (+)-magnolone

Synthesis of optically pure 2,3,4-trisubstituted tetrahydrofurans is described employing a two-step Michael-Evans aldol cyclization strategy. The approach is successfully applied for the total synthesis of furano lignan natural product (+)-magnolone.     

Studies toward the total synthesis of azaspiracids: synthesis of the FGHI ring domain

Synthesis of the FGHI ring domain of azaspiracids, the causative agents for a new type of shellfish poisoning, azaspiracid poisoning (AZP), has been achieved. The synthesis features dithiane anion-epoxide coupling for convergent fragment assembly.     

Enantioselective total synthesis of sacrolide A

An enantioselective total synthesis of sacrolide A, an antimicrobial and cytotoxic fourteen-membered macrolactonic oxylipin isolated from an edible freshwater cyanobacterium, has been accomplished from a known carboxylic acid in 20% overall yield by a concise ten-step sequence. The key transformations include chiral oxazolidinone-based diastereoselective installation of two hydroxy-bearing stereocenters, the Horner–Wadsworth–Emmons olefination to construct the full carbon skeleton, and the Shiina macrolactonization to establish the fourteen-membered macrolide structure.     

Discovery of potent cell migration inhibitors through total synthesis: lessons from structure-activity studies of (+)-migrastatin

Synthesis of highly active migrastatin-based tumor migration cell inhibitors has been accomplished. Our flexible and concise total synthesis of migrastatin has allowed us to explore otherwise inaccessible migrastatin-derived structural motifs. This effort has resulted in the discovery of analogues with tumor cell migration inhibitory activity 3 orders of magnitude higher than that of the natural product.     

Stereoselective total synthesis of rubrenolide and rubrynolide

The stereoselective total synthesis of rubrenolide and rubrynolide has been accomplished successfully. The synthetic strategy involves Evans alkylation and asymmetric CBS reduction to establish the required stereogenic centers. Other key steps involve Horner–Wadsworth–Emmons (HWE) olefination to construct the side chain, alkynylation to introduce terminal unsaturation in the side chain, and TEMPO-BAIB-mediated lactonization.     

Progress toward the total synthesis of (+)-aldosterone: synthesis of the A-D rings

[reaction: see text] Synthesis of the A-D rings of the cortical hormone (+)-aldosterone is described. The key step incorporates a chiral tether in a type 2 intramolecular Diels-Alder reaction that establishes the absolute configuration of four contiguous asymmetric centers. This approach provides an efficient route for either enantiomer of the steroid skeleton.     

The first total synthesis of concanamycin f (concanolide a)

A highly stereoselective total synthesis of the macrolide antibiotic concanamycin F (1), a specific and potent inhibitor of vacuolar H(+)-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 18-membered tetraenic lactone and beta-hydroxyl hemiacetal side chain subunits. The C1-C19 18-membered lactone aldehyde 4 was synthesized through the intermolecular Stille coupling of the C5-C13 vinyl iodide 24 and the C14-C19 vinyl stannane 25, followed by construction of the C1-C4 diene and macrolactonization. Synthesis of 4 via a second convergent route including the esterification of the C1-C13 vinyl iodide 45 and the C14-C19 vinyl stannane 47 followed by the intramolecular Stille coupling was also realized. The highly stereoselective aldol coupling of 4 and the C20-C28 ethyl ketone 5 followed by desilylation provided 1 which was identical with natural concanamycin F.     

First stereoselective total synthesis of pectinolide H

The stereoselective total synthesis of bio-active pectinolide H (1) is described. Midland’s asymmetric reduction, Sharpless dihydroxylation reactions are involved in generating the stereogenic centers at C-4′, C-5 and C-1′. Other key steps in the synthesis are Sonogashira cross coupling, Z-selective Still–Gennari olefination, one-pot acetonide deprotection–lactonization, and Lindlar’s reaction. This offers a distinctive strategy for the synthesis of γ-lactones.     

Synthesis of myo-inositol derivatives required for the total synthesis of surugatoxin, prosurugatoxin, and neosurugatoxin

Two myo-inositol derivatives (4) and (5), required for the total synthesis of surugatoxin, prosurugatoxin, and neosurugatoxin, were prepared. Synthesis of (+/-)-2,3-O-cyclohexylidene-4,5-O-isopropylidene-1-O-methoxymethyl-myo-i nositol (4) was achieved from (+/-)-1-O-benzoyl-2,3-O-cyclohexylidene-4,5-O-isopropylidene-myo-inosito l (6) in 4 steps, and (-)-2,3-O-cyclohexylidene-1,4-di-O-methoxymethyl-5-O-[2',3',4'-tri-O-ace tyl- beta-D-xylopyranosyl]-myo-inositol (5) was synthesized from (+/-)-1-O-benzoyl-2,3-O-cyclohexylidene-5,6-O-isopropylidene-myo-inosito l (12) in 7 steps.     

Short eight-steps total synthesis of racemic asteriscunolide C

A concise total synthesis of racemic asteriscunolide C in eight steps has been described starting from neopentane diol involving an efficient Yamaguchi esterification using an aldehyde-acid, intramolecular Horner–Wittig–Emmons olefination, and a late stage ring-closing metathesis to construct the strained 11-membered ring with one Z- and two E-double bonds.     

Enantiospecific formal total synthesis of (+)-dihydrokawain-5-ol

Abstract

Formal total synthesis of dihydrokawain-5-ol is accomplished starting from tartaric acid. Key reactions include Horner–Wadsworth–Emmons olefination, sodium borohydride mediated stereoselective reduction, orthogonal protection and deprotection of alcohols and ring closing metathesis.     

Asymmetric synthesis of actinoidic acid derivatives

Synthesis of fully protected actinoidic acid derivative 3 and selectively protected biaryl bisamino acid 4, intermediates for vancomycin total synthesis, are reported.     

The Woodward-Doering/Rabe-Kindler total synthesis of quinine: setting the record straight

In 1918, Paul Rabe and Karl Kindler reported the three-step conversion of d-quinotoxine into quinine. In 1944 Robert B. Woodward and William von Eggers Doering reported the total synthesis of homomeroquinene and d-quinotoxine from 7-hydroxyisoquinoline. Based on the transformations by Rabe and Kindler, Woodward and Doering asserted the "Total Synthesis of Quinine" (the title of their 1944 and 1945 papers). In 2000 and 2001, Gilbert Stork concluded that the claim by Woodward and Doering is a "myth" because they had synthesized only homomeroquinene and d-quinotoxine; no synthetic quinine had been made in Cambridge. In fact, Rabe and Kindler never published the experimental details of their conversion of d-quinotoxine into quinine. This Review presents the results of a detailed examination of the synthesis of cinchona alkaloids, and previously unpublished material combined with unpublished material and numerous interviews give insight into the lives of the personalities in this nearly 100-year saga.     

A short regiospecific total synthesis of furoventalene,a marine natural benzofuran

Synthesis of a naturally occurring irregular isoprenoid benzofuran, furoventalene ( 3 ), has been achieved in high yield via the nickel catalyzed coupling of 4-methyl-3-penten-1-ylmagnesium bromide ( 1 ) with 3-methyl-6-chlorobenzofuran ( 2 ).     

Synthesis of some analogues of (±)gelliusine F, (±)gelliusine E,and total synthesis of 2,2-di(6′-bromo-3′-indolyl)ethylamine

Synthesis of some analogues of indole based marine alkaloid (±)gelliusine F, (±)gelliusine E, and total synthesis of 2,2-di(6′-bromo-3′-indolyl)ethylamine are reported.     

Studies directed towards the total synthesis of botcinic acid, the revised structure of botcinolide: synthesis of the highly substituted tetrahydropyran moiety

Synthesis of the highly substituted polyoxygenated tetrahydropyran ring of botcinic acid, the revised structure of botcinolide is achieved using, as key steps, a highly stereoselective aldol reaction of the titanium enolate from a lactate-derived chiral ketone and a stereoselective dihydroxylation.     

Catalytic synthesis and reactions of nitrogen heterocycles (Review)

Studies at the Latvian Institute of Organic Synthesis and literature data from 1984–1994 on organic catalysis in the chemistry of N-heterocycles are reviewed. 77 to prospects for further developments in catalytic reactions of N-heterocycles are examined.     

Design and synthesis of novel pyrazol-3ylthiazoles

Biheterocyclic compounds in recent years have gained a significant importance in medicinal chemistry. In this paper the synthesis of novel pyrazol-3ylthiazoles through Vilsmeier–Haack reaction using 2-amino thiazoles as precursors is described. Synthesis of twelve new derivatives was accomplished with moderate yield (70–76%). Structures of all the newly synthesized compounds were characterized by spectral (¹H NMR, ¹³C NMR, IR, LC–MS) and elemental analyses.     

Ring-expansion approaches for the total synthesis of salimabromide

We describe the evolution of a synthetic strategy for the construction of the marine polyketide salimabromide. Combining a bicyclo[3.1.0]hexan-2-one ring-expansion to build up a functionalized naphthalene and an unprecedented rearrangement/cyclization cascade, enabled synthesis of a dearomatized tricyclic subunit of the target compound. Alternatively, an intramolecular keteniminium [2 + 2]-cycloaddition and subsequent Baeyer–Villiger ring-expansion gave access to the sterically encumbered architecture of salimabromide. Sequential oxidation of the carbon framework finally enabled the total synthesis of this unusual natural product.     

A Negishi cross-coupling reaction enables the total synthesis of (+)-stachyflin

We present a full account on the development of the total synthesis of the antiviral meroterpenoid (+)-stachyflin. The decalin subunit is rapidly accessed by an exo-selective Diels–Alder reaction, whereas the isonindolinone was synthesized via a highly efficient and practical de novo route starting from dimedone. A challenging sp²–sp³ Negishi cross-coupling reaction enabled construction of the crucial C15–C16 bond that connects the arene with the decalin subunit. For the final installation of the cis-decalin framework, a Lewis acid-catalyzed cyclization was applied.