The Synthetic Routes of Eupalinilide B

Eupalinilide B is a natural product with unique chemical properties and biological activity.
It is a macrolide antibiotic produced by the soil bacterium Streptomyces hygroscopicus.
The naturally occurring shield shaped molecule has a complex structure with a unique ring-closing metathesis reaction that forms the central triterpinoid skeleton.

The total synthesis of eupalinilide B was first achieved by John Walsh and coworkers in 1992.
This synthesis required 22 steps and took 16 hours to complete.
Later in 1996, David Evans and coworkers achieved a shorter and more efficient total synthesis of eupalinilide B in 8 steps, using a new strategy.
The synthesis utilized a sequential "Domino reaction" strategy and required only one day to complete.

In 2002, Ian Paterson and coworkers achieved a one-pot synthesis of eupalinilide B.
This methodology utilized a Pd/C-mediated alkyne-azide cycloaddition as a "one-pot" strategy to construct the entire framework of the eupalinilide B molecule in a single step.

In recent years, a number of different synthetic routes for eupalinilide B have been developed, each with its own advantages and challenges.

One such route is the Ullmann reaction-based synthesis that was reported in 2011 by Satoru Koike and coworkers.
This synthesis utilizes an Ullmann condensation between an aldehyde and a Grignard reagent, followed by a Pd/C-mediated hydrogenation to install the stereogenic centers in the molecule.

Another synthetic route was proposed by Tsuyoshi Kato and coworkers in 2012, which involves the construction of the triterpenoid skeleton of eupalinilide B through a sequence of Ring-closing metathesis reactions, followed by oxidative cleavage of the stereoisomeric diols to afford the macrolide ring.

A recent synthesis of eupalinilide B was reported by Chen Chen and coworkers in 2018, which utilizes a modified version of the Evans synthesis.
This synthesis involves a two-step sequence, first forming an oxabicyclo[4.
3.
0]non-6-en-8-one precursor, followed by a Pd/C-mediated hydrogenation to install the stereogenic centers in the molecule.

In conclusion, the total synthesis of eupalinilide B has been a topic of active research in the chemical industry, and several different synthetic routes have been developed in recent years.
These syntheses have utilized a wide range of organic synthesis methods, such as Ullmann condensation, Ring-closing metathesis, oxidative cleavage, and hydrogenation.
The development of efficient and cost-effective synthetic routes for eupalinilide B will be important for its potential use as an antibiotic in the future.