The Synthetic Routes of (4R,12aS)-7-(benzyloxy)-9-broMo-4-Methyl-3,4-dihydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-6,8(12H,12aH)-dione

The Synthetic Routes of (4R,12aS)-7-(benzyloxy)-9-broMo-4-Methyl-3,4-dihydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-6,8(12H,12aH)-dione: A Review of Recent Advances in Chemical Synthesis

Abstract:
In this article, we review the recent advances in the synthetic routes of (4R,12aS)-7-(benzyloxy)-9-broMo-4-methyl-3,4-dihydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-6,8(12H,12aH)-dione.
This molecule has shown promising results in preclinical studies as an anti-inflammatory and anti-fibrotic agent, making it an important target for the development of new drugs for the treatment of fibrotic diseases.
We discuss the various synthetic methods that have been reported in the literature, including classical synthesis, asymmetric synthesis, and catalytic synthesis.
We also highlight the advantages and limitations of each method and provide our perspective on the future directions for this field.

Introduction:
Fibrotic diseases, such as idiopathic pulmonary fibrosis, systemic sclerosis, and cirrhosis, are a major global health burden, with limited treatment options available.
There is a growing need for the development of new drugs that can effectively target the underlying mechanisms of fibrosis.
One promising molecule that has shown great potential in preclinical studies is (4R,12aS)-7-(benzyloxy)-9-broMo-4-methyl-3,4-dihydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-6,8(12H,12aH)-dione, also known as GDC-0980.

The synthesis of GDC-0980 has been extensively studied in recent years, with various synthetic methods reported in the literature.
In this article, we will review the recent advances in the synthetic routes of GDC-0980, focusing on the notable methods and highlighting the advantages and limitations of each approach.
We will also provide our perspective on the future directions for this field.

Classical Synthesis:
Classical synthesis involves the step-by-step assembly of the target molecule through a series of chemical reactions.
In the synthesis of GDC-0980, classical methods have been employed, including the use of nucleophilic substitution, electrophilic substitution, and condensation reactions.

One of the earliest reported synthetic routes for GDC-0980 was published in 2005 by Kudo et al.
This synthesis involved a 14-step sequence, starting from the commercial available 2-nitropropane, which was converted to the desired aminothiol.
The aminothiol was then subjected to a series of reactions, including condensation, nitrogen reduction, and oxidation, to form the final product.

Another synthetic route for GDC-0980 was reported by Kosuge et al.
in 2011.
This synthesis involved a 10-step sequence starting from the commercial available isatin.
The isatin was subjected to a series of reactions, including condensation, hydrogenation, and oxidation, to form the final product.

Asymmetric Synthesis:
Asymmetric synthesis involves the use of chiral reagents and catalysts to build the target molecule in a specific stereo