Along with the development of new analytical instruments and techniques over the past 30 years, a variety of marine alkaloids have been isolated and characterized from natural resources. Further chemical and biological studies on these marine alkaloids should contribute to a deeper understanding of their roles in nature. Also, intensive studies involving the comprehensive evaluation of these molecules may lead to the creation of a new field in bioscience.


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Top Heterocycl Chem (2006) 6: 181-214 DOI 10.1007/7081_032 © Springer-Verlag Berlin Heidelberg 2006 Published online: 7 April 2006

Synthetic Studies on Heterocyclic Antibiotics Containing Nitrogen Atoms

Hiromasa Kiyota

Graduate School of Agricultural Science, Tohoku University,

1-1 Tsutsumidori-Amamiyamachi, 981-8555 Aoba-ku Sendai, Japan

[email protected]

1 Introduction 182

2 Glutarimide Antibiotics, the Cycloheximide Family 183

2.1 Cycloheximide and Derivatives 183

2.1.1 Stereoisomers of Cycloheximide 183

2.1.2 Hydroxylated Derivatives, Streptovitacins A and C2, and E-73 186

2.1.3 Aromatic Ring Derivatives, Actiphenol and Actiketal 188

2.1.4 Aliphatic Derivative, Streptimidone 189

2.1.5 Lactam Derivative, Epiderstatin 191

2.2 Macrolactones and Hydroxy Acids 191

2.2.1 Total Synthesis of Migrastatin 193

2.2.2 Migrastatin Analogs 195

2.2.3 Synthetic Studies of Dorrigocin A 195

3 Antimycins and Related Antibiotics 196

3.1 Early Syntheses of Antimycin A3b 196

3.1.1 Kinoshita's First Synthesis of Antimycin A3b 196

3.1.2 Synthetic Studies in the 1980s 198

3.2 Recent Syntheses of Antimycins 200

3.2.1 Oritani's Synthesis of (-)-Antimycin A3b 200

3.2.2 Tsunoda's Synthesis of Antimycin A3a and A3b 200

3.3 Synthesis of UKs 202

4 Tabtoxins 204

4.1 Tabtoxinine-^-lactam (T^L), a Tobacco Wildfire Disease Toxin 204

4.2 Early Synthesis of Tabtoxin and Related Compounds 205

4.2.1 Rapoport's Synthesis of Tabtoxinine-5-Lactam 205

4.2.2 Baldwin's Synthesis of Tabtoxin and (±)-T£L 206

4.3 Recent Synthesis of T£L 208

5 Conclusion 209

References 211

Abstract A variety of heterocyclic antibiotics and phytotoxins have been found to date. Total and semi-synthesis of these natural products and related analogous compounds are essential for the elucidation of structure-activity relationships and the development of useful agrochemicals and medicines. Early and recent examples are described, including synthetic studies of glutarimide antibiotics (cycloheximide and related aliphatic and macrolactone derivatives), antimycins (antimycin A and related diolides), and tabtoxins (amino acids with a hydroxy ^-lactam ring).

Keywords Antibiotics • Antimycins • Glutarimides • Tabtoxins • Total synthesis

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