Webinar: Efficient Synthesis of Complex Pyridone Intermediates: A Dolutegravir Starting Material Is Prepared as an Exemplar

The Medicines for All Institute’s (M4ALL’s) mission is to improve access to affordable medicines by reducing the cost of active pharmaceutical ingredients (APIs) and key raw materials which can be major cost drivers in treating infectious diseases in the developing world.  In collaboration with the Bill & Melinda Gates Foundation, M4ALL has demonstrated cost-effective processes for APIs, starting materials, and key intermediates for many critical medicines. In support of M4ALL’s mission, M4ALL will host a webinar to introduce our research on “Continuous Synthesis of the Pyridone In Route to Dolutegravir” on June 11, 2019.  Participants must register for the webinar through the registration website by June 11, 2019.  The purpose of this webinar is to provide technical information on M4ALL’s recently developed continuous flow pyridone synthesis. The process is flexible and should have application towards a few APIs, including cabotegravir and bictegravir. Our objective is to encourage interested parties to adopt our technology. M4ALL recently reported a continuous synthesis of Dolutegravir (Ziegler, et al. ACIEE 2018) wherein an intensified and generalizable continuous synthesis of complex pyridones was described. Since this report, we have continued to improve the approach. Using Dolutegravir as an example, we compare our continuous process to the previous patented batch process.

M4ALL will release a process development report in June 2019 upon request.

Market Summary: According to the CHAI HIV Market Report, Issue 9 (September 2018) the market for dolutegravir API is conservatively projected as 50 MT in 2019, 100 MT in 2020, 150 MT in 2021 and 200 MT in 2022.

Administrative: All administrative and technical questions should be directed to m4all@vcu.edu. Please refer to the notice number (M4ALL-DTG-2019-1) in all correspondences. This announcement is not a request for proposals. M4ALL will not provide reimbursement for costs incurred in responding to this notice. Respondents are advised that M4ALL will respond within 48 hours.

Note: M4ALL will be attending CPhI China in Shanghai during June 18-20, 2019. If interested in meeting with M4ALL at CPhI, please contact Dr. Rodger Stringham at rwstringham@vcu.edu.


Webinar: An Efficient Synthesis of (R)-3-aminobutanol: A Significant Cost Driver in the Synthesis of Dolutegravir

The Medicines for All Institute’s (M4ALL’s) mission is to improve access to affordable medicines by reducing the cost of active pharmaceutical ingredients (APIs) and key raw materials which can be major cost drivers in treating infectious diseases in the developing world. In collaboration with the Bill & Melinda Gates Foundation, M4ALL has demonstrated cost-effective processes for APIs, starting materials, and key intermediates for many critical medicines.

In support of M4ALL’s mission, M4ALL will host a webinar to introduce our research on “An Efficient Synthesis (R)-3-aminobutanol in Route to Dolutegravir” on November 18, 2019.  Participants may register for the webinar through the registration website until the date of the webinar.  The purpose of this webinar is to provide technical information on M4ALL’s one-step protocol for the preparation of (R)-3-aminobutan-2-ol from commercially available D-β-homoalanine. Using materials originating from the chiral pool, asymmetric methodologies and chiral resolution procedures are avoided. A simple one-step process leverages low-cost commodity materials and results in a 70% cost reduction of the aminoalcohol and a 19% cost reduction in the final API. M4ALL have previously reported a continuous process for producing the pyridone intermediate and we now disclose a low-cost process to access the optically active aminoalcohol. Our objective is to encourage interested parties to adopt our improved technologies.

M4ALL will release a process development report in November 2019 upon request.

Market Summary: DTG is becoming a first-line therapy for HIV patients in more than 50-low to middle-income countries. The market for dolutegravir API is conservatively projected to reach 250 MT by 2022.

Administrative: All administrative and technical questions should be directed to m4all@vcu.edu. Please refer to the notice number (M4ALL-DTG-2019-2) in all correspondences. This announcement is not a request for proposals. M4ALL will not provide reimbursement for costs incurred in responding to this notice. Respondents are advised that M4ALL will respond within 48 hours.


Webinar: An Efficient Synthesis of 5-Fluorocytosine from Acyclic Precursors

The Medicines for All Institute’s (M4ALL’s) mission is to improve access to affordable medicines by reducing the cost of active pharmaceutical ingredients (APIs) and key raw materials which can be major cost drivers for Global Health medications.  Supported by grants from the Bill & Melinda Gates Foundation, M4ALL has demonstrated cost-effective processes for APIs, starting materials, and key intermediates for nevirapine, tenofovir hydroxypropyladenine, dolutegravir, and is currently working on emtricitabine, lamuvidine, and tenofovir disoproxil fumarate.   As an interim deliverable in connection with its work on emtricitabine, M4ALL will host a taped webinar to introduce our research on “Efficient Synthesis of 5-Fluorocytosine from Acyclic Precursors” on January 23 and February 11, 2019.  Participants must register through the registration website to obtain the webinar link.  The purpose of this webinar is to provide technical information and further details on M4ALL’s innovative research on 5-fluorocytosine and the opportunity for any interested stakeholders to adopt and implement our technology.

Efficient Synthesis of 5-Fluorocytosine from Acyclic Precursors Abstract: A key intermediate in the synthesis of emtricitabine (FTC) is the nucleobase 5-fluorocytosine (5FC).  A new route to 5FC has been developed starting from inexpensive acyclic precursors. The route uses low cost raw materials and introduces the fluorine via sodium fluoride. Techno-economic analysis reveals the cost of chemical inputs is reduced by 40-60 percent. The overall isolated yield is 48%.

M4ALL will start releasing our 5FC process development report in January 2019 upon request.

Market Summary*: Exports of FTC from India to Africa currently total 120 MT/year.  This corresponds to 1.6 million patients, largely in South Africa. Treatment prices for FTC are around $20 per patient per year, compared to 3TC at $15 pppy.  Recent increases in cytosine prices (80% since January 2018) will narrow this gap. Work presented here has the potential to reduce the prices for 5FC, making FTC treatment less costly than 3TC.  If this happens the FTC market may be expected to grow dramatically. (These are not guaranteed outcomes.)

Administrative: All administrative and technical questions should be directed to m4all@vcu.edu. Please refer to the notice number (M4ALL-5FC-2019-1) in all correspondences. This announcement is not a request for proposals. M4ALL will not provide reimbursement for costs incurred in responding to this notice. Respondents are advised that M4ALL will respond within 48 hours.

*Prices are weighted averages from India Import/Export Database January 2017 – October 2018.  Shipments of < 100 kg excluded from analysis.