A Stereoselective Synthesis of (+)-Herboxidiene/GEX1A

A stereoselective synthesis of (+)-herboxidiene is described. The convergent synthesis utilized a Suzuki cross-coupling reaction to assemble the key segments. The synthesis of the functionalized tetrahydropyran ring utilized an Achmatowicz reaction as the key step. The synthesis of the C10−C19 segment was accomplished using Brown’s crotylboration, asymmetric alkylation, and a stereoselective allylic chlorination reactions

Synthesis of Enantiomerically Pure Anti-Aldols: A Highly Stereoselective Ester-Derived Titanium Enolate Aldol Reaction

Synthesis of Enantiomerically Pure Anti-Aldols:  A Highly Stereoselective Ester-Derived Titanium Enolate Aldol Reactio

Enantioselective Synthesis of (−)-Platensimycin Oxatetracyclic Core by Using an Intramolecular Diels−Alder Reaction

An enantioselective route to the oxatetracyclic core of (−)-platensimycin (1) has been investigated by using an intramolecular Diels−Alder reaction as the key step. The thermal reaction of E/Z mixture (1:1) provided oxatetracyclic core 2 from the E-diene and the Z-diene was recovered unchanged. The Diels−Alder substrate was conveniently assembled in optically active form with use of (S)-carvone as the starting material

Total Synthesis of (+)-Polyoxin J^†

Stereoselective total synthesis of (+)-polyoxin J is described. The synthesis was achieved in a convergent manner by coupling protected thymine polyoxin C (19) and 5-O-carbamoyl polyoxamic acid 27 and subsequent removal of the protecting groups. The key steps of the synthesis of protected thymine polyoxin C involved the stereoselective electrophilic epoxidation of E-allyl alcohol 7 derived from isopropylidene d-ribose derivative 5, followed by regioselective epoxide opening of 8 and conversion of resulting azido diol 9 to protected thymine polyoxin C (19). Protected polyoxamic acid 27 was synthesized stereoselectively by utilizing Sharpless epoxidation of tartrate-derived allylic alcohol 20 followed by a regioselective epoxide ring opening with diisopropoxytitanium diazide

Enantioselective Total Synthesis of (+)-Amphidinolide T1

An enantioselective first total syntheis of amphidinolide T1 (1) is described. Amphidinolide T1 (1), a 19-membered macrolide isolated from Amphidinium sp., has shown potent antitumor properties against a variety of NCI tumor cell lines. The synthesis is convergent and involves the assembly of C1−C10 segment 2 and C11−C21 segment 3 by an oxocarbenium ion-mediated alkylation and Yamaguchi macrolactonization sequence. The synthesis of fragment 2 involves an efficient cross metathesis and hydrogenation sequence between the terminal olefins of 5 and 6 to form the C4−C5 carbon−carbon bond. Enol ether 4 is designed to be the surrogate of fragment 3 where the sensitive C16-exo-methylene and the C13-hydroxyl group were protected as the bromoether derivative during the Lewis acid-catalyzed alkylation process. Both stereocenters in fragment 5 as well as the C2 and C3 stereocenters in fragment 4 are accessed by a highly diastereoselective ester-derived titanium enolate-mediated syn-aldol reaction. The bromoether derivative 24 was unraveled at the final stage of the synthesis, providing (+)-amphidinolide T1

An Asymmetric Total Synthesis of Brevisamide

An enantioselective synthesis of marine alkaloid brevisamide was accomplished in a convergent manner. The synthesis utilized an enantioselective hetero-Diels−Alder reaction which sets three chiral centers in compound 11. The synthesis also features a modified Wolff−Kishner reduction, Rubottom oxidation, and Suzuki−Miyaura coupling to furnish brevisamide

Assignment of Absolute Stereochemistry and Total Synthesis of (−)-Spongidepsin

An enantioselective total synthesis of (−)-spongidepsin (2) and elucidation of the absolute stereochemistry of its four stereocenters are described. Spongidepsin (2), a 13-membered depsipeptide isolated from the Vanuatu marine sponge Spongia sp., has shown potent antitumor properties against a variety of NCI tumor cell lines. Our synthesis is convergent, and the absolute stereochemistry of four of the five chiral centers was assigned through synthesis

Total Synthesis and Revision of C6 Stereochemistry of (+)-Amphidinolide W

An enantioselective first total synthesis and structural revision of the cytotoxic natural product amphidinolide W is described. We initially investigated a ring-closing metathesis based synthetic strategy to form the 12-membered macrocycle. This strategy was unsuccessful as it led to formation of a 17-membered macrocycle. Subsequently, we explored an alternative strategy that involved cross-metathesis followed by a Yamaguchi macrolactonization reaction sequence utilizing the same key intermediates. This strategy led to the synthesis of amphidinolide W. The synthesis was carried out in a convergent manner, and four of the five stereogenic centers in amphidinolide W were set by asymmetric synthesis. The synthesis features Sharpless asymmetric dihydroxylation, diastereoselective alkylation, efficient cross-metathesis of functionalized substrates, and novel functional group transformations using selective lipase-catalyzed hydrolysis of the primary acetate group. Of particular note, the C6 absolute stereochemistry of amphidinolide W has now been revised through our synthesis

High-Yield Synthesis of Fluorinated Benzothiazolyl Sulfones: General Synthons for Fluoro-Julia Olefinations

General, high-yield tandem electrophilic fluorination and modified Julia olefination for the synthesis of fluoro olefins is reported. A series of α-fluoro 1,3-benzothiazol-2-yl sulfone-based synthons were synthesized via deprotonation−fluorination. Of critical importance for high-yield fluorinations were heterogeneous reaction conditions, as under homogeneous conditions only starting sulfones were recovered. The α-fluoro 1,3-benzothiazol-2-yl sulfones so obtained were subjected to condensations with a variety of aldehydes and ketones to afford high yields of regiospecifically fluorinated olefins

Assignment of Absolute Stereochemistry and Total Synthesis of (−)-Spongidepsin

An enantioselective total synthesis of (−)-spongidepsin (2) and elucidation of the absolute stereochemistry of its four stereocenters are described. Spongidepsin (2), a 13-membered depsipeptide isolated from the Vanuatu marine sponge Spongia sp., has shown potent antitumor properties against a variety of NCI tumor cell lines. Our synthesis is convergent, and the absolute stereochemistry of four of the five chiral centers was assigned through synthesis