Lavendamycin is a naturally occurring chemical compound discovered in

fermentation Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...

broth of the

soil bacterium Soil microbiology is the study of microorganisms in soil, their functions, and how they affect soil properties. It is believed that between two and four billion years ago, the first ancient bacteria and microorganisms came about on Earth's ocea ...

Streptomyces lavendulae ''Streptomyces lavendulae'' is a species of bacteria from the genus ''Streptomyces''. It is isolated from soils globally and is known for its production of medically useful biologically active metabolites. To see a photo of this organism clic ...

''. Lavendamycin has

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

properties and

anti-proliferative Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

effects against several

cancer cell lines Cancer cells are cells that divide continually, forming solid tumors or flooding the blood with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, and these d ...

. The use of lavendamycin as a

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

agent in

cancer therapy Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal ble ...

failed due to poor water solubility and non-specific

cytotoxicity Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

. The study of lavendamycin-based

analogs Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analog ...

designed to overcome these liabilities has been an area of research. __TOC__

Discovery

Lavendamycin was first discovered in 1981 by Doyle et al., who isolated it from ''Streptomyces lavendulae''. As the compound failed to crystallize, a direct characterization of the molecular structure with X-ray crystallography was not possible. Careful analysis using NMR, IR, and UV-VIS spectroscopy and

mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is use ...

allowed the assignment of the pentacyclic structure consisting of a β-carboline unit and a quinolinequinone unit.

Total syntheses

The attractive biological properties and complex structure of lavendamycin have made it the target of a large number of

total syntheses Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes ...

. Within a few years after the structural elucidation by Doyle et al., the research groups of Kende, Hibino, Rao, and Boger had already developed total syntheses for the compound independently of one another. The discovery that analogs of lavendamycin are potent inhibitors of HIV

reverse transcriptase A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, ...

led to further attempts in the 90s to develop efficient routes to lavendamycin. However, large numbers of steps, low overall yields (0.5–2%) or poorly available starting materials make these syntheses unattractive for further systematic development of lavendamycin and its analogs. Notably, total syntheses by Behforouz and Nissen offer flexible construction of the lavendamycin scaffold at high yields.

References

Streptomyces Beta-Carbolines Carboxylic acids Antibiotics {{organic-compound-stub