Sporolides A and B are polycyclic

macrolides The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. M ...

extracted from the obligate

marine bacterium Marine prokaryotes are marine bacteria and marine archaea. They are defined by their habitat as prokaryotes that live in marine environments, that is, in the saltwater of seas or oceans or the brackish water of coastal estuaries. All cellula ...

'' Salinispora tropica'', which is found in

ocean sediment Marine sediment, or ocean sediment, or seafloor sediment, are deposits of insoluble particles that have accumulated on the seafloor. These particles have their origins in soil and rocks and have been transported from the land to the sea, main ...

. They are composed of a chlorinated cyclopenta ndene ring and a cyclohexenone moiety. They were the second group of compounds (after salinosporamide A) isolated from ''

Salinispora ''Salinispora'' is a genus of obligately aerobic, gram-positive, non-acid-fast bacteria belonging to the family of Micromonosporaceae. They are heterotrophic, non-motile, and obligately grow under high osmotic/ ionic-strength conditions. ...

'', and were said to indicate the potential of marine actinomycetes as a source of novel secondary

metabolites In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

. The structures and absolute stereochemistries of both metabolites were elucidated using a combination of NMR spectroscopy and X-ray crystallography. The complex aromatic structure of the sporolides was hypothesized to be derived from an unstable nine-membered ring

enediyne In organic chemistry, enediynes are organic compounds containing two triple bonds and one double bond. Enediynes are most notable for their limited use as antitumor antibiotics (known as enediyne anticancer antibiotics). They are efficient at ...

precursor, which could undergo

Bergman cyclization The Masamune-Bergman cyclization or Masamune-Bergman reaction or Masamune-Bergman cycloaromatization is an organic reaction and more specifically a rearrangement reaction taking place when an enediyne is heated in presence of a suitable hydrogen ...

to generate a para-benzyne intermediate. Nucleophilic attack by chloride would account for the 1:1 mixture of sporolide A and B and for the single chlorine in these enediyne-derived natural products. This proposed mechanism was demonstrated in laboratory experiments,

Biosynthesis

The biosynthesis of sporolide A and B is related to that of enediynes such as

dynemicin A Dynemicin A is an anti-cancer enediyne drug. It displays properties which illustrate promise for cancer treatments, but still requires further research. History and background Dynemicin A was first isolated from the soil in the Gujarat State ...

and is proposed to proceed as shown below.

Chemical synthesis

The first

total synthesis 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 i ...

of sporolide B was reported by

K. C. Nicolaou Kyriacos Costa Nicolaou ( el, Κυριάκος Κ. Νικολάου; born July 5, 1946) is a Cypriot-American chemist known for his research in the area of natural products total synthesis. He is currently Harry C. and Olga K. Wiess Professor of ...

's group and used a highly stereoselective and convergent strategy that involved two cycloaddition reactions. The first was a ruthenium-catalyzed intermolecular +2+2cycloaddition reaction between two acetylenic units, A and B, and the second a thermally induced intramolecular +2cycloaddition reaction between an

o-quinone 1,2-Benzoquinone, also called ''ortho''-benzoquinone, is an organic compound with formula . It is one of the two isomers of quinone, the other being 1,4-benzoquinone. It is a red volatile solid that is soluble in water and ethyl ether. It is r ...

and the tetrasubstituted

olefin In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...

within the intermediate, forming the macrocyclic structure of the target product.

References

{{Reflist Macrolides Cyclohexenes Heterocyclic compounds with 7 or more rings Oxygen heterocycles Epoxides