Direct entry to erythronolides via a cyclic bis[allene]

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Antibiotic macrolides are complex molecules.
• Their synthesis is difficult, hindering efforts to combat antibiotic resistance.
• Existing semi- or total synthesis methods face significant challenges.

Purpose of the Study:

• To develop a novel and efficient strategy for synthesizing macrolide antibiotics.
• To create a versatile macrocyclic intermediate for generating diverse erythronolide congeners.
• To overcome the limitations of current synthetic approaches for macrolides.

Main Methods:

• Preparation of a complex yet tractable macrocyclic precursor.
• Transformation of the macrocycle into various erythronolide congeners.
• Utilizing short synthetic routes from the macrocycle intermediate.

Main Results:

• A new synthetic strategy was successfully developed.
• The macrocycle intermediate was efficiently prepared in a longest linear sequence of 11 steps.
• Erythronolides were synthesized in three or fewer steps from the macrocycle.

Conclusions:

• The described strategy offers a tractable route to complex macrolides.
• The macrocycle serves as a valuable intermediate for accessing diverse erythronolide structures.
• This approach provides new potential for exploring macrolide antibiotic structure-activity relationships and combating resistance.