The Discovery Process Of Sucralose

1、 Unexpected discovery: fatal mishearing in the laboratory (1975-1976)

1. Background preparation

Research institution: Tate&Lyle and University of London collaborate to develop a new insecticide.

Initial goal: To modify sucrose molecules as pesticide carriers (using sugar molecules to attract insects).

Theoretical basis: Modifying sucrose structure through chlorination reaction to enhance lipid solubility and penetrate insect cuticle.

2. Historical misoperation

Key figure: Shashikant Phadnis, an Indian researcher.

Dramatic Moment (1976):

Colleague Leslie Hough requested Phadnis to "test" a sucrose chloride product (TGS, trichlorogalactose).

Phadnis misheard as "taste" and directly tasted the powder.

→ Discovered extremely sweet (sweetness ≈ 600 times sucrose), with no bitterness and safe and sound.

📌  Scientific contingency: The compound (TGS) is actually an intermediate in the synthetic pathway, not the target pesticide.

2、 Structural optimization: from TGS to sucralose (1976-1980)

1. Key breakthrough in molecular modification

Results of Improvement Scheme for TGS Defects in Primitive Molecules

Trichlorogalactose has poor chemical stability and selective chlorination locking of 4,1 ', 6' - trichloro-4,1 ', 6' - deoxygalactose (sucralose)

Easy hydrolysis failure → Protective groups control reaction sites

Core improvements:

→ Accurately replace the three hydroxyl groups (- OH) in sucrose molecules with chlorine atoms (- Cl) at positions C4 (glucosyl)+C1 '&C6' (fructosyl).

Chlorine atoms act as' molecular anchors':

✅  Blocking enzyme hydrolysis (not metabolized by the human body).

✅  Twisted conformation → high-intensity activation of sweet taste receptors (hT1R2/hT1R3).

2. Significant leap in physical and chemical performance

Stability: Acid and alkali resistance (pH 2-8), high temperature resistance (no decomposition after baking at 200 ℃).

Solubility: 28g/100mL water (25 ℃), far exceeding other high potency sweeteners.

3、 Security Verification and Industrialization (1980-1999)

1. The most rigorous security assessment in history

Research scale: Over 100 animal/human experiments, with a total cost of 200 million US dollars.

Core conclusion:

→ No metabolism: Molecules that are too large (C₁₂H₁₉Cl₃O₈) cannot pass through the intestinal wall, and more than 85% are excreted in their original form.

→ Non toxicity: No evidence of teratogenicity, carcinogenicity, or mutagenicity (NOAEL: 1500mg/kg/day).

→ No blood glucose effect: GI=0, not recognized by insulin.

2. Global approval milestones

Year: Key Actions by Country/Institution

1991 Canada's first approval (table sweetener)

In 1998, the US FDA approved it for use in 15 categories of food

2004 EU EFSA comprehensive license (daily allowable intake of 15mg/kg)

In 2011, the Chinese Ministry of Health included it in the "Standard for the Use of Food Additives"

4、 Scientific significance and industrial impact

1. Innovation in molecular design paradigm

Inspiration: accidental discovery → rational modification (chlorine atom localization substitution).

Derivative technology: Based on the "structure sweetness effect relationship" model of sucralose, promote the development of subsequent sweeteners (such as Advantame).

2. Business success

Market size in 2023: $1.8 billion (accounting for 35% of the global high power sweeteners).

Application scenario: From Diet Coke with Splenda ®） To pharmaceuticals (masking agents).

5、 Discovery Process Diagram

mermaid

Copy Code

graph LR

A [Research on Sucrose Chlorination] -->B {1976 Phadnis misheard instruction}

B -->| Mistasted TGS | C [found extremely sweet and non-toxic]

C -->D [Structural analysis: 4,1 '', 6 '' - Trichloro substitution]

D -->E [Optimize synthesis path]

E -->F [100 safety tests]

F -->G [1991 Canada First Admission]

G -->H [Global Food Industry Revolution]

Key insights

The birth of sucralose confirms the classic law in the history of science:

Chance favors only prepared minds

——Its value lies in the researchers' keen ability to capture abnormal phenomena and invest ten years of hard work to achieve:

Molecular Precision Engineering (Chlorine Atom Localization Substitution Technology)

Construction of Safety System (Empirical Study of Metabolic Inert)

Thus, a laboratory slip of the tongue ultimately reshaped the sweet landscape of the global food industry.