Total Synthesis of the Potent HIF‑1 Inhibitory Antitumor Natural Product, (8<i>R</i>)‑Mycothiazole, via Baldwin–Lee CsF/CuI sp³–sp²‑Stille Cross-Coupling. Confirmation of the Crews Reassignment

A convenient asymmetric total synthesis of the potent HIF-1 inhibitory antitumor natural product, (−)- or (+)-(8<i>R</i>)-mycothiazole (<b>1</b>), is described. Not only does our synthesis confirm the 2006 structural reassignment made by Crews (Crews, P., et al. J. Nat. Prod. 2006, 69, 145), it revises the [α]_D data previously reported for this molecule in MeOH from −13.7° to +42.3°. The newly developed route to (8<i>R</i>)-<b>1</b> sets the C(8)–OH stereocenter via Sharpless AE/2,3-epoxy alcohol reductive ring opening and utilizes two Baldwin–Lee CsF/cat. CuI Stille cross-coupling reactions with vinylstannanes <b>8</b> and <b>3</b> to efficiently elaborate the C(1)–C(4) and C(14)–C(18) sectors

Asymmetric Total Synthesis and Formal Total Synthesis of the Antitumor Sesquiterpenoid (+)-Eremantholide A

A new asymmetric total synthesis of (+)-eremantholide A is reported in which a Hoveyda−Grubbs ring-closing metathesis (RCM) reaction is used to assemble the nine-membered oxonin ring, and an enolate alkylation between the 3(2H)-furanone 2 and O-triflate 3 is exploited for C(9)−C(10) bond construction. An Evans asymmetric aldol reaction and a Sharpless asymmetric epoxidation served to stereoselectively install the C(6), C(7), and C(8) stereocenters of the target structure

Synthetic Route to the GE3 Cyclodepsipeptide

A reasonably efficient [2 + 2 + 2] fragment condensation strategy has been developed for assembling the cyclodepsipeptide sector of GE3 that involves 5−7. A Carpino HATU-mediated macrolactamization was used to close the 19-membered cyclodepsipeptide ring

A New Stereocontrolled Synthetic Route to (−)-Echinosporin from d-Glucose via Padwa Allenylsulfone [3 + 2]-Anionic Cycloadditive Elimination

A new formal total synthesis of (−)-echinosporin has been developed based upon the Padwa [3 + 2]-cycloadditive elimination reaction of allenylsulfone 4 with the d-glucose-derived enone 14 which provides cycloadduct 12

A New Stereocontrolled Total Synthesis of the Mast Cell Inhibitory Alkaloid, (+)-Monanchorin, via the Wittig Reaction of a Stabilized Ylide with a Cyclic Guanidine Hemiaminal

An asymmetric total synthesis of the mast cell inhibitor (+)-monanchorin is reported in which a Sharpless AD on <b>11</b> and a cyclic sulfate ring opening with an azide feature as key steps. After further manipulation, a novel guanidine-controlled ester reduction provided the guanidine-hemiaminal <b>25</b> which underwent Wittig olefination to give <b>27</b>. Hydrogenation and a second guanidine-controlled reduction of the ester in <b>28</b>, to obtain aldehyde <b>29</b>, then set up a trifluoroacetic acid mediated cyclization to give (+)-monanchorin TFA salt

A New Stereocontrolled Synthetic Route to (−)-Echinosporin from d-Glucose via Padwa Allenylsulfone [3 + 2]-Anionic Cycloadditive Elimination

A new formal total synthesis of (−)-echinosporin has been developed based upon the Padwa [3 + 2]-cycloadditive elimination reaction of allenylsulfone <b>4</b> with the d-glucose-derived enone <b>14</b> which provides cycloadduct <b>12</b>

A Short Synthetic Pathway to a Fully-Functionalized Southern Hemisphere of the Antitumor Macrolide Bryostatin 1

An 18-step asymmetric synthesis of the bryostatin 1 “southern hemisphere” fragment (1) has been developed. Key steps include an aldol reaction between 6 and 7 and a dehydration to establish the (E)-exocyclic alkene in 2 and a stereoselective Luche reduction and protection with TESOTf to access 1

A Synthetic Strategy for the Cyclodepsipeptide Core of the Antitumor Antibiotic Verucopeptin

An efficient [2 + 2 + 2]-fragment condensation strategy is described for obtaining the cyclodepsipeptide core of verucopeptin. The 19-membered macrocycle was established through a Carpino HATU mediated macrolactamization, which proceeded in good yield under high-dilution conditions

Total Synthesis of the GRP78-Downregulatory Macrolide (+)-Prunustatin A, the Immunosuppressant (+)-SW-163A, and a JBIR-04 Diastereoisomer That Confirms JBIR-04 Has Nonidentical Stereochemistry to (+)-Prunustatin A

A unified total synthesis of the GRP78-downregulator (+)-prunustatin A and the immunosuppressant (+)-SW-163A based upon [1 + 1 + 1 + 1]-fragment condensation and macrolactonization between O(4) and C(5) is herein described. Sharpless asymmetric dihydroxylation was used to set the C(2) stereocenter present in both targets. In like fashion, coupling of the (+)-prunustatin A macrolide amine with benzoic acid furnished a JBIR-04 diastereoisomer whose NMR spectra did not match those of JBIR-04, thus confirming that it has different stereochemistry than (+)-prunustatin A

New, Abridged Pathway to Masamune's “Southern Hemisphere” Intermediate for the Total Synthesis of Bryostatin 7

The “Southern Hemisphere” intermediate 2, used by Masamune and co-workers for their asymmetric total synthesis of bryostatin 7 (1), has been synthesized from (E)-1,4-hexadiene (11) by a 24-step pathway that has a longest linear sequence of only 20 steps. This is the shortest synthesis of 2 so far recorded, and moreover, it is fully stereocontrolled