Seijiro Hosokawa

Name:

Organization: Waseda University

Department: Department of Applied Chemistry

Title:

Chemicals
References

Stereoselective Synthesis of Tabtoxinine-β-lactam by Using the Vinylogous Mukaiyama Aldol Reaction with Acetate-Type Vinylketene Silyl N,O-Acetal and α-Keto-β-lactam

Co-reporter:Hirotaka Ejima, Fumihiro Wakita, Ryo Imamura, Takuya Kato, and Seijiro Hosokawa

Organic Letters May 19, 2017 Volume 19(Issue 10) pp:

Publication Date(Web):May 4, 2017

DOI:10.1021/acs.orglett.7b00814

Stereoselective total synthesis of tabtoxinine-β-lactam has been achieved. The vinylogous Mukaiyama aldol reaction with vinylketene silyl N,O-acetal and α-keto-β-lactam proceeded to afford the adduct possessing a TβL-skeleton with a tert-alcohol in high yield and stereoselectivity. Stereoselective introduction of the amino group has been accomplished by azidation at the α position of the imide followed by hydrogenolysis. A straightforward method to achieve the potent inhibitor of glutamine synthetase, possessing both α-hydroxy-β-lactam and α-amino acid moieties, has been established.

Remote Asymmetric Induction Using Acetate-Type Vinylketene Silyl N,O-Acetals

Co-reporter:Naoya Sagawa, Haruka Sato, and Seijiro Hosokawa

Organic Letters 2017 Volume 19(Issue 1) pp:198-201

Publication Date(Web):December 13, 2016

DOI:10.1021/acs.orglett.6b03476

Remote asymmetric induction by the vinylogous Mukaiyama aldol reaction using the acetate-type vinylketene silyl N,O-acetal possessing a chiral auxiliary has been achieved. The silyl N,O-acetal derived from crotonate and l-valine afforded the O-silylated 5R- and 5S-adducts selectively by treatment with SnCl4 and BF3·OEt2, respectively. The SnCl4-mediated isomerization of silyl dienol ether was found, and the resulting major isomer showed high reactivity to give γ-adduct in high stereoselectivity.

Syn Selective Vinylogous Mukaiyama Aldol Reaction Using Z,E-Vinylketene N,O-Acetal with Acetals

Co-reporter:Naoya Sagawa, Hiroki Moriya, and Seijiro Hosokawa

Organic Letters 2017 Volume 19(Issue 1) pp:250-253

Publication Date(Web):December 21, 2016

DOI:10.1021/acs.orglett.6b03549

Stereoselective vinylogous Mukaiyama aldol reactions using the Z,E-vinylketene silyl N,O-acetal possessing a chiral auxiliary, derived from (E)-3-pentenoic acid and l-valine, have been achieved. The reaction proceeded smoothly to give a syn adduct in high stereoselectivity. Since the products possess structures including δ-alkoxy-γ-methyl-α,β-unsaturated imide, this reaction would be applicable to synthesize polyketides in a short procedure.

Stereoselective Alkylation of the Vinylketene Silyl N,O-Acetal and Its Application to the Synthesis of Mycocerosic Acid

Co-reporter:Tatsuya Nakamura, Kei Kubota, Takanori Ieki, and Seijiro Hosokawa

Organic Letters 2016 Volume 18(Issue 1) pp:132-135

Publication Date(Web):December 16, 2015

DOI:10.1021/acs.orglett.5b03422

Stereoselective alkylation of the vinylketene silyl N,O-acetal possessing a chiral auxiliary has been achieved by using activated alkyl halides including allyl iodides, benzyl iodides, and propargyl iodide with Ag(I) ion in the presence of BF3·OEt2. The reaction proceeded to give reduced polyketides in high stereoselectivity. The synthesis of mycocerosic acid, a component of the cell envelope of Mycobacterium tuberculosis, has been accomplished by this methodology. During the synthetic studies, 2-methylbenzimidazole was found to be a bulky proton source which worked in the presence of liquid ammonia.

Synthetic Studies on Aculeximycin: Synthesis of C24–C40 Segment by Kobayashi Aldolization and Epoxide Rearrangements

Co-reporter:Takuya Kato, Tomohiko Sato, Yuki Kashiwagi, and Seijiro Hosokawa

Organic Letters 2015 Volume 17(Issue 9) pp:2274-2277

Publication Date(Web):April 23, 2015

DOI:10.1021/acs.orglett.5b00965

Stereoselective synthesis of the C24–C40 segment of aculeximycin has been achieved by using the Kobayashi aldol reactions and epoxy-opening rearrangement reactions. The C33–C40 segment was synthesized by the Kobayashi aldol reaction followed by epoxidation and Jung rearrangement of epoxide 9, while the C25–C32 segment was constructed by the Kobayashi aldol reaction followed by epoxidation and the epoxy-opening rearrangement reaction of epoxide 13. These segments were connected by the aldol reaction and the sequential dehydration, reduction, and conversion of ethyl ester to ethyl ketone to give the C24–C40 segment 1. All stereogenic centers were constructed by substrate-controlled stereoselective reactions.

Stereoselective Acylation of the E,E-Vinylketene Silyl N,O-Acetal and Its Application to the Synthesis of Khafrefungin

Co-reporter:Yuta Takahashi, Maiko Otsuka, Mio Harachi, Yuki Mukaeda, and Seijiro Hosokawa

Organic Letters 2014 Volume 16(Issue 16) pp:4106-4109

Publication Date(Web):July 29, 2014

DOI:10.1021/ol501805j

Stereoselective acylation of the E,E-vinylketene silyl N,O-acetal possessing a chiral auxiliary has been achieved by using acid anhydrides and SnCl4. Acid anhydrides having alkyl chains gave the adducts in excellent stereoselectivity. The formal synthesis of khafrefungin has been accomplished by the methodology.

Total Synthesis of Hibarimicinone, a v-Src Tyrosine Kinase Inhibitor Possessing the Pseudo-Dimer Structure of Tetracycline

Co-reporter:Kuniaki Tatsuta

The Chemical Record 2014 Volume 14( Issue 1) pp:28-40

Publication Date(Web):

DOI:10.1002/tcr.201300020

Abstract

The total synthesis of hibarimicinone, a potent v-Src tyrosine kinase inhibitor possessing thirteen stereogenic centers and an axial chirality, has been achieved. The key step to constructing the eight-ring skeleton was the double Michael–Dieckmann-type cyclization (Hauser annulation) using a thiolactone pseudo-dimer. These synthetic studies indicated the efficiency of the thiolactone-employed route to synthesize the multiply functionalized polycyclic compounds. The ABCD-ring moiety including the bridging ether was constructed by a strategy including oxidation of the C-ring hydroquinone and the subsequent transfer of the oxidation stage to the neighboring ring. The atropisomer of hibarimicinone was also synthesized to confirm the structure of the natural product.

Concise Synthesis of Reduced Propionates by Stereoselective Reductions Combined with the Kobayashi Reaction

Co-reporter:Tatsuya Nakamura, Mio Harachi, Takaaki Kano, Yuki Mukaeda, and Seijiro Hosokawa

Organic Letters 2013 Volume 15(Issue 12) pp:3170-3173

Publication Date(Web):June 11, 2013

DOI:10.1021/ol401406m

A concise and straightforward synthesis of 2,4,6-trimethyloctanoates was established by using the sequence of the vinylogous Mukaiyama aldol reaction and regio- and stereoselective reduction reactions. All isomers were obtained selectively in a few steps. The short step synthesis of septoriamycin A, an antimalarial and antileishmanial agent, has been achieved by this methodology.

syn-Selective Kobayashi Aldol Reaction Using Acetals

Co-reporter:Hiroyuki Tsukada, Yuki Mukaeda, and Seijiro Hosokawa

Organic Letters 2013 Volume 15(Issue 3) pp:678-681

Publication Date(Web):January 18, 2013

DOI:10.1021/ol303519y

The Kobayashi aldol reaction has been used to construct anti-aldol products by remote stereoinduction. Since the product of the Kobayashi aldol reaction has a typical polyketide structure, this reaction has been applied to the total synthesis of natural products. By varying this reaction, it was found that the reaction with acetals in the presence of Lewis acid proceeded to give syn adducts in high stereoselectivity. This is the first example of the stereoselective reaction of the chiral dienol ether and acetals.

Syn-Selective Kobayashi Aldol Reaction Using the E,E-Vinylketene Silyl N,O-Acetal

Co-reporter:Yuki Mukaeda, Takuya Kato, and Seijiro Hosokawa

Organic Letters 2012 Volume 14(Issue 20) pp:5298-5301

Publication Date(Web):October 4, 2012

DOI:10.1021/ol3024677

The Kobayashi aldol reaction is one of the most powerful methods to synthesize the polyketide skeleton and has been applied to the total synthesis of natural products. This methodology has been used to construct anti-aldol products, and only a few precedents on the syn-selective Kobayashi aldol reaction are known. A syn-selective Kobayashi aldol reaction by using the E,E-vinylketene silyl N,O-acetal and an excess amount of Lewis acid is presented.

The first total synthesis of hibarimicinone, a potent v-Src tyrosine kinase inhibitor

Co-reporter:Kuniaki Tatsuta, Tomohiro Fukuda, Tatsuya Ishimori, Rearu Yachi, Shinpei Yoshida, Hiroshi Hashimoto, Seijiro Hosokawa

Tetrahedron Letters 2012 Volume 53(Issue 4) pp:422-425

Publication Date(Web):25 January 2012

DOI:10.1016/j.tetlet.2011.11.062

The first total synthesis of hibarimicinone has been achieved. The polyhydroxydecalin moieties (AB and GH rings) have been synthesized from sulfonylenone 4 derived from d-arabinose. The chiral biaryl 20 was coupled with two polyhydroxydecalins 11 by Michael–Dieckmann type condensation to give the eight rings system. Aromatization and oxidation with Ag+ gave quinone 24, and the subsequential transannular etheration gave the hibarimicinone skeleton. Deprotection and tautomerization were performed in one pot to give hibarimicinone (1).

Total Synthesis of an Anti-Helicobacter pylori Agent, ActinopyroneA

Co-reporter:Seijiro Hosokawa Dr.;Kazuya Yokota;Keisuke Imamura;Yasuaki Suzuki;Masataka Kawarasaki ;Kuniaki Tatsuta Dr.

Chemistry – An Asian Journal 2008 Volume 3( Issue 8-9) pp:1415-1421

Publication Date(Web):

DOI:10.1002/asia.200800109

Abstract

Actinopyrone A, an anti-Helicobacter pylori agent, was synthesized in nine steps from a silyl dienol ether. A vinylogous anti-aldol was stereoselectively synthesized by our developed remote stereoinduction methodology; coupling of this with a sulfone and a phosphonate species led to the construction of a vinylpyrone compound. This was submitted to reductive de-conjugation to give actinopyrone A. The absolute stereochemistry of actinopyrone A was determined to have the configuration 14R,15R.