The headmistress of Haberdashers' Monmouth school for girls, and newly-appointed president of the UK's independent girls' schools association, says she has nothing against boys.
In fact, she believes the world is made of a growing number of new men who are much more likely to wash nappies, job share and work part-time. But Dr Despontin, who won the 2003 Promethean Award for school leadership in a secondary school in Wales, still believes the two are like chalk and cheese in the classroom.
She said: "Girls and boys should not be taught together. They way they respond, react and develop educationally are different. Girls who went on to fantastic careers tell me they wouldn't have done it if boys had been in their classroom."
With 32 years' experience in teaching, including a period working in a home for disturbed teenage girls, the teacher from the Welsh valleys knows her stuff. She believes in strong female role models and her physics department is entirely staffed by them.
"When girls leave our school, they are well-qualified, confident young women free to consider every imaginable career avenue," she said.
"Later, they will undoubtedly face important decisions about their worklifefamily balance, but they will have confidence enough to consider these pragmatically and be comfortable enough about who they are to live with their decisions."
Dr Despontin's strong leadership skills in single-sex education are to be put to the test nationally. Born in Caerphilly, she has been appointed president of the Girls' Schools Association (GSA), one of five professional associations in the Independent Schools Council. Dr Despontin, 55, took over from former president Clarissa Farr at the start of this month.
She predicts 2006 will be a time for putting independent schools and single-sex schools on the map. But she says a shortage of teachers ready to take on headships needs to be tackled.
She said: "I had to be nudged into becoming a headmistress. It is a difficult job but also exciting."
The new president also plans to pursue more unity in the independent sector. Her past teaching posts include Willows high school in Cardiff and King's school in Macclesfield.