Stereoselective total synthesis of reveromycin B and C19-epi-reveromycin B

Our studies toward the total synthesis of the reveromycin family of natural products are described herein. Our synthetic approach is efficient, stereocontrolled, and convergent and has resulted in the first synthesis of reveromycin B (4) and C19-epi-reveromycin B (55). Key steps of this successful strategy include: a modified Negishi coupling (construction of C7-C8 bond) and a Kishi-Nozaki reaction (construction of C19-C20 bond), which were employed in the attachment of the target side chains. The key building blocks for the total synthesis were thus defined as vinyl iodide 6, alkyne 7, and alkyne 8. Our synthesis illustrates the utility of the modified Negishi coupling for the construction of complex dienes, confirms the proposed stereochemistry of reveromycins and paves the way for the preparation of designed analogues for biological study.     

Stereoselective synthesis of (+)-radicamine B

A simple and efficient stereoselective synthesis of naturally occurring pyrrolidine alkaloid, radicamine B has been accomplished in 13 steps from the commercially available starting materials with an overall yield of 9.75%. The synthesis utilizes Sharpless asymmetric epoxidation and Horner-Wadsworth-Emmons (HWE) olefination as key steps.     

Stereoselective synthesis of methyl monate C

[Structure: see text] The stereoselective synthesis of methyl monate C 2 is described using as a key step an ene-intramolecular modified Sakurai cyclization (IMSC) reaction to prepare tetrahydropyran 5. An asymmetric allylic alkylation, followed by a cross-metathesis, enables the insertion of the right-hand side chain.     

Stereoselective total synthesis of Patulolide C

Abstract

Stereoselective total synthesis of Patulolide C has been accomplished from easily available and inexpensive (S)-chiral epoxide. The key steps involved in the concise synthesis of Patulolide C utilizes ring opening of chiral epoxide, cleavage of 1,2-diol, deprotection of benzyl ether of hydroxyl acid and Yamaguchi macrolactonisation dilution conditions as key steps. The advantage of this method include inexpensive starting material, mild reaction conditions and high purity of products.     

Stereoselective total synthesis of ieodomycin C

A concise stereoselective synthesis of the marine natural product ieodomycin C (3) has been achieved from commercially available pyridinium-1-sulfonate (8) in eight linear steps and 14% overall yield. The key synthetic steps included a B-alkyl Suzuki–Miyaura cross-coupling reaction and an Evans–Nagao acetate aldol reaction. The same synthetic sequence was used for preparing the enantiomer of ieodomycin C (3). Our efforts confirmed the structure of the antibacterial natural product 3.     

Stereoselective synthesis of the cis-275B decahydroquinoline ring system

The Diels-Alder precursor was constructed from readily available d-glutamic acid utilizing a series of functional group transformations. The stereocenter of the amino acid provided the desired stereochemistry at C2 and diastereoselectively directed the intramolecular Diels-Alder cyclization. This simultaneously generated the three remaining stereocenters and yielded a bicyclic intermediate with all four stereocenters of the target decahydroquinoline 275B.     

Stereoselective synthesis of the cytotoxic macrolide aspergillide B

A total, stereoselective synthesis of the cytotoxic macrolide aspergillide B has been performed. A cross metathesis and a C-glycosidation via a Mukaiyama-type aldol reaction were key features of the synthesis. The macrocyclic lactone ring was created by means of the Yamaguchi procedure.     

Stereoselective synthesis of the C1-C20 segment of the microsclerodermins A and B

An enantioselective route for the synthesis of key fragment C1-C20 resident in microsclerodermins A and B is described. The route features deoxygenative rearrangement of an hydroxy-alkynoate and a highly enantio- and diastereo-controled iterative dihydroxylation as key reactions, starting from S-(−)-citronellol.     

Stereoselective synthesis of the C9-C19 fragment of lyngbyaloside B and C via ether transfer

A stereoselective synthesis of the C9-C19 fragment of lyngbyaloside B and C highlighted, by an extension of our ether transfer methodology, enables the formation of tertiary ethers. 2-Naphthylmethyl ethers have been shown to proceed efficiently through ether transfer with high stereoselectivity and are easily deprotected by DDQ oxidation. Variation of the workup conditions results in the stereoselective formation of syn-1,3-diol mono- or diethers.     

Stereoselective total synthesis of synparvolide B and epi-synparvolide A

Stereoselective total synthesis of synparvolide B and epi-synparvolide A has been achieved following a convergent approach. Noyori asymmetric Transfer Hydrogenation of ketone and Wadsworth-Emmons olefination reaction are the key steps involved.     

Stereoselective synthesis of methyl 7-dihydro-trioxacarcinoside B

A stereoselective synthesis of 7-dihydro-triocacarcinose B, a branched octose from the quinocyclines, has been achieved. The biocatalytic resolution of a Baylis-Hillman adduct and a subsequent ring-closing metathesis were used to assemble the molecular framework. Subsequent key steps were a highly stereoselective epoxidation and a regio- and stereoselective opening of the epoxide by allyl alcohol and HClO4 to introduce the C(3)-OH group in protected form. The 7-dihydro-triocacarcinose B could be converted into the corresponding 1,7-anhydrosugar.     

Stereoselective synthesis of acortatarins a and B

Acortatarins A and B have been synthesized via stereoselective spirocyclizations of glycals. Mercury-mediated spirocyclization of a pyrrole monoalcohol side chain leads to acortatarin A. Glycal epoxidation and reductive spirocyclization of a pyrrole dialdehyde side chain leads to acortatarin B. Acid equilibration and crystallographic analysis indicate that acortatarin B is a contrathermodynamic spiroketal with distinct ring conformations compared to acortatarin A.     

Stereoselective total synthesis of (+)-sapinofuranone B

Two approaches for the total synthesis of (+)-sapinofuranone B have been described. The first strategy utilizes the methodology developed earlier in our group to get the chiral propargyl alcohol and the second strategy involves generation of threo-1,2-diol derivative by diastereoselective and enantioselective addition of [(Z)-γ-methoxymethoxyallyl]diisopinocampheylborane onto aldehyde and cross metathesis as the key steps.     

Stereoselective synthesis of the C(1)-C(13) segment of dolabelide B

The efficient construction of the C₁-C₁₃ segment of dolabelide B is described. A key element of the synthesis entails BITIP catalyzed asymmetric methallylation to establish the C₇ stereocenter, which was then used to direct the stereoselective installation of the C₉ and C₁₁ centers through Evans reduction and 1,5-anti aldol condensation, respectively.     

Stereoselective total synthesis of Ieodomycin A and B

The stereoselective total synthesis of Ieodomycin A and B, bioactive secondary metabolites from marine sources with potent anti-microbial activity was achieved starting from commercially available geranial. The key steps involved in the synthetic sequence of Ieodomycin A and B are the Sharpless asymmetric epoxidation, the formation of a β-ketoester, and the 1,3-anti reduction. The synthesis of C-3 epimer of Ieodomycin A and B was also accomplished in good yields.     

Stereoselective synthesis of simplactone B via Prins cyclisation

The synthesis of simplactone B has been achieved through a series of nine steps in 85% overall yield using Prins cyclisation as the key step with high stereochemical control.     

Stereoselective synthesis of the C21C27 fragment of the phorboxazoles

A stereoselective synthesis of the C21C27 fragment of phorboxazoles A and B was achieved in 12 linear steps via an intramolecular cyclization induced by mercury acetate, to afford a functionalized tetrahydropyran.     

Stereoselective synthesis of pachastrissamine (jaspine B)

A stereoselective synthesis in enantiopure form of the natural anhydrophytosphingosine pachastrissamine (jaspine B), a metabolite isolated from sponges, is described. The chiral epoxide (R)-glycidol was the starting material. Key steps of this synthesis are a Sharpless asymmetric epoxidation, an intramolecular stereospecific epoxide opening mediated by a trichloroacetimidate group, and the formation of a tetrahydrofuran ring via intramolecular nucleophilic displacement.     

Stereoselective synthesis of the C1–C12 fragment of the thuggacins

A concise asymmetric synthesis of the C1–C12 fragment of the antibacterial natural product thuggacins has been achieved. The stereochemistry of this fragment was established efficiently via stereoselective reduction and Evans-aldol condensation. Hanztsch’s method and a Horner–Wadsworth–Emmnons reaction were employed for thiazole formation and the construction of the E-α,β-unsaturated double bond.     

Stereoselective synthesis of (+)-pericosine B and (+)-pericosine C using ring closing metathesis approach

Stereoselective synthesis of (+)-pericosine B and (+)-pericosine C were achieved from d-ribose using RCM and RCEYM as key steps.