4H-Thieno[2,3-b]thiopyran-4-one,5,6-dihydro-6-methyl-, 7,7-dioxide, (6S) NEW

The compound 4H-Thieno[2,3-b]thiopyran-4-one, 5,6-dihydro-6-methyl-, 7,7-dioxide, (6S) is a key chiral intermediate in the synthesis of dorzolamide (a carbonic anhydrase inhibitor used to treat glaucoma). Here's a concise breakdown:

Chemical Structure & Features

Core Skeleton:

• Bicyclic system: Thieno[2,3-b]thiopyran (fusion of thiophene + thiopyran rings).

• 7,7-Dioxide: Both sulfur atoms oxidized to sulfones (critical for bioactivity).

• 5,6-Dihydro: Partial saturation at the 5-6 bond.

• 4-one: Ketone at position 4.

• 6-Methyl: Methyl group at C6.

• (6S): Chiral center with S-configuration at C6 (essential for drug efficacy).

  Systematic Name:

• *(6S)-5,6-Dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-4-one 7,7-dioxide*

• CAS Registry: 130693-82-2 (specific to the (6S)-enantiomer).

Primary Chemical Use

• Synthesis of Dorzolamide:
  This compound is the immediate precursor to dorzolamide’s core structure. In the final steps:

• *(4S,6S)-4-(Ethylamino)-5,6-dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide*.

• The ketone (C4=O) undergoes reductive amination with ethylamine.

• Introduces the ethylamino group (–NHCH₂CH₃) at C4.

• Yields dorzolamide’s active pharmacophore:

Key Properties & Handling

• Chiral Purity: The (6S)-configuration must be preserved to match dorzolamide’s stereochemistry.

• Reactivity:

• Ketone at C4 is highly reactive for nucleophilic addition (e.g., amines).

• Sulfone groups enhance electrophilicity and binding to carbonic anhydrase.

• Stability: Sensitive to epimerization at C6; requires controlled conditions (low temperature, inert atmosphere).

• Handling: Typically handled as a solid (crystalline) under anhydrous conditions.

Why It Matters

• Pharmaceutical Role: Enables stereoselective production of dorzolamide, ensuring clinical efficacy.

• Synthetic Challenge: Asymmetric synthesis/purification of (6S)-isomer is critical for regulatory compliance.

• Patent Significance: Protected under dorzolamide manufacturing patents (e.g., Merck & Co.).

For reference:
Final Step:

This intermediate is not biologically active itself but is indispensable for constructing the therapeutic molecule.